Decoding The MAO-A Gene: What It Means For Your Health

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Decoding The MAO-A Gene: What It Means For Your Health

Date of Content: May 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article does not include all possible risk variants for the MAO-A gene and is for informational purposes only. This article is not intended for diagnosis. Please talk to a healthcare professional if you have symptoms associated with these variants.

What is The MAO-A Gene?

The MAO-A gene, on the X chromosome (Xp11.3), encodes the enzyme monoamine oxidase A, which is essential for breaking down certain neurotransmitters in the brain. The monoamine oxidase A (MAO-A), plays a crucial role in regulating the levels of neurotransmitters such as serotonin, norepinephrine, and dopamine. These neurotransmitters are vital for mood regulation, arousal, and emotional responses.

Common Polymorphisms

The MAO-A R297R synonymous polymorphism is caused by a specific single nucleotide polymorphism (SNP) in the monoamine oxidase A (MAO-A) gene, where the nucleotide at position 941 in the DNA sequence can vary. This SNP is also known by its reference SNP ID, rs6323 G>T.

Impact on Health and Behavior:

  • Aggression and Behavioral Traits: Variations in the MAO-A gene, including the R297R polymorphism, have been studied for their role in aggressive behavior and other psychiatric conditions. Research suggests that specific variants of the MAO-A gene can influence susceptibility to stress and aggression.
  • MAO-A Activity: The R297R  and other polymorphisms are associated with variations in the MAO-A enzyme activity. Some studies indicate that individuals with certain variants may have higher or lower MAO-A activity, which can affect the breakdown of neurotransmitters and subsequently influence mood and behavior.

More on this below.

Which Aspects of Your Health Is Influenced by MAO-A Gene?

Mood Regulation

The MAO-A enzyme breaks down neurotransmitters like serotonin, norepinephrine, and dopamine, which are critical for mood regulation. Abnormal activity of MAO-A can lead to imbalances in these neurotransmitters, contributing to mood disorders such as depression and anxiety. Individuals with specific variants of the MAO-A gene may be more prone to experiencing these conditions.

A 2009 study investigated how genetic polymorphisms in different genes influenced placebo responsiveness in major depressive disorder. Placebo (a treatment with no active ingredient) response varies greatly between individuals. Researchers feel this response works through brain pathways related to rewards controlled by chemicals called monoamines (like serotonin and dopamine). Since genetics strongly influences these chemicals’ activity in the brain, researchers hypothesized that common genetic variations (polymorphisms) that affect the activity of these chemicals would be related to how much a person improves when treated with a placebo for major depressive disorder. Findings revealed that subjects with MAO-A polymorphisms coding for the higher activity form of the enzyme (rs 6323 genotype GT or GG) exhibited a significantly lower placebo response than those with other genotypes.

Behavioral Control

MAO-A activity influences behaviors related to impulse control and aggression. Genetic variations in the MAO-A gene, sometimes called the “warrior gene,” have been associated with increased aggression and antisocial behavior, especially under stressful conditions. These behavioral tendencies can impact social interactions and overall mental health.

In a 2008 study combining psychology and behavioral economics, researchers found that aggression increased in intensity and frequency as provocation levels rose, particularly among individuals with the low-activity MAOA (MAOA-L) variant. Participants punished those they believed had taken money from them by administering varying amounts of spicy sauce. Results showed that the MAOA genotype significantly affected aggressive behavior, especially under high provocation.

Stress Response

The MAO-A gene plays a role in how the body responds to stress. Variants of the MAO-A gene can affect the breakdown of neurotransmitters involved in the stress response, potentially leading to heightened stress sensitivity and altered coping mechanisms. It can influence susceptibility to stress-related disorders.

A 2018 study investigated the influence of stressful life events on aggression among Chinese adolescents in the context of gene polymorphisms. The two genes considered were COMT and MAO-A. Results showed that adolescents carrying the lower-activity-causing MAOA T-allele of the T941G polymorphism showed more aggression with increased interpersonal problems. Additionally, adolescents with the lower activity genotype of the COMT Ala22/72Ser polymorphism and MAOA  T941G T-allele exhibited more aggression under high academic pressure.

Cognitive Function

The MAO-A gene indirectly affects cognitive function by regulating the levels of neurotransmitters that are important for cognitive processes, including attention, memory, and learning. Imbalances in neurotransmitter levels due to altered MAO-A activity can impair cognitive abilities and contribute to neurological conditions.

A 2018 study investigated the association between MAOA gene polymorphisms and attention deficit hyperactivity disorder (ADHD) in Korean children. ADHD, a common neurodevelopmental disorder, is thought to be linked to dopaminergic, serotonergic, and noradrenergic pathways, with MAOA playing a crucial role in neurotransmitter catabolism. Results showed significant associations between the rs6323 G>T polymorphism and ADHD in girls, with the TT genotype acting as a protective factor.

Also read: A Walkthrough of the LifeDNA Personality and Cognition Report

Response to Medications

Individuals with different MAO-A gene variants may respond differently to certain medications, especially those affecting neurotransmitter levels, such as antidepressants (including MAO inhibitors). Understanding one’s MAO-A gene status can help personalize treatment for mental health conditions.

Get your LifeDNA Methylation Genes report to understand your MAO-A gene polymorphisms in more detail. 

Vitamin B2 and MAO-A Enzyme

Vitamin B2, or riboflavin, is a water-soluble vitamin that is vital for many cellular processes. It functions mainly as a precursor to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN and FAD are critical for the activity of various flavoproteins. Flavoproteins are a group of proteins that contain a flavin molecule and are mainly involved in reactions related to energy production and detox. These flavoproteins play a significant role in redox reactions. Redox reactions are highly specialized reactions that help animals, including humans, break down complex compounds into usable energy (respiration).

Riboflavin, as a precursor to FMN and FAD, indirectly influences the activity of MAO-A. MAO-A is also a flavoprotein. Like other flavoproteins, it requires FAD as a cofactor for its enzymatic activity. Thus, adequate levels of riboflavin are essential for the optimal functioning of MAO-A.

  • Riboflavin ensures the availability of FAD, which is necessary for the catalytic activity of MAO-A.

Some studies suggest that riboflavin might influence the expression of genes involved in redox regulation, potentially affecting MAO-A activity.

Managing Implications of MAO-A Gene Polymorphisms

Regular Monitoring

Regular psychiatric evaluations and monitoring are crucial for managing symptoms effectively. These check-ups allow healthcare providers to adjust treatment plans as needed, ensuring that the therapeutic approach remains effective and responsive to changes in the individual’s condition.

Therapy

Cognitive Behavioral Therapy (CBT) is effective in managing symptoms of depression, anxiety, and aggression by helping individuals change negative thought patterns. Dialectical Behavior Therapy (DBT) can be beneficial for those with mood regulation issues and impulsive behavior. Family therapy can also provide significant support by improving family dynamics and fostering a supportive environment.

Stress Management

Techniques such as mindfulness, meditation, and relaxation exercises can significantly reduce stress and improve emotional regulation. These practices help individuals manage their responses to stressors, which can mitigate the impact of MAO-A gene variations on behavior and mood.

Diet

Maintaining a balanced diet abundant in fruits, vegetables, whole grains, and lean proteins supports overall brain health. A healthy diet can positively influence neurotransmitter function and mood stability.

Exercise

Regular physical activity is an excellent way to manage stress, improve mood, and reduce symptoms of anxiety and depression. Exercise boosts the production of endorphins and other neurotransmitters that enhance mood and overall mental health.

Sleep Hygiene

Ensuring adequate and regular sleep is vital for maintaining mood and mental health. Establishing a consistent sleep schedule and creating a restful sleep environment can help manage the symptoms associated with MAO-A gene variations.

Genetic Counseling

Genetic counseling provides valuable information about the implications of MAO-A gene variations. Counselors can support individuals and families in understanding these variations and making informed decisions about management and treatment options.

Support Groups

Joining support groups can provide a sense of community and shared experience for individuals with MAO-A gene variations. These groups offer emotional support and practical advice from others facing similar challenges, which can be incredibly beneficial.

Regular Check-ups

Scheduling consistent follow-up appointments with healthcare providers ensures regular monitoring of the symptoms and adjusting the treatment plans as necessary. Regular check-ups also help promptly address changes in the individual’s condition and maintain effective management strategies.

Medication

Antidepressants such as SSRIs and SNRIs can help manage mood disorders linked to MAO-A variations by balancing neurotransmitter levels. MAO inhibitors (MAOIs) might be prescribed in some cases, though they require careful dietary management due to potential side effects. Mood stabilizers can also be beneficial for those experiencing mood swings and aggression, helping to maintain emotional stability.

References

Customer Reviews

Christopher Devlin
Christopher Devlin
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I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
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Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
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It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
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*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

The LifeDNA Methylation Genes Report: A Walkthrough

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The LifeDNA Methylation Genes Report: A Walkthrough

Date of Content: May 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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The Methylation Cycle in Brief

The methylation cycle is a complex series of biochemical reactions involving various enzymes. To simplify, we will outline the core concept of this cycle to provide a clear context for the roles of specific genes discussed later in this article. This foundational understanding will enhance our exploration of how these genes influence the cycle and various aspects of health and disease.

  • Central to the methylation cycle is the conversion of homocysteine to methionine by the enzyme methionine synthase. 
  • This reaction requires methylcobalamin (a form of vitamin B12) and 5-methyltetrahydrofolate (produced from folate by the enzyme MTHFR). 
  • Methionine can then be converted to S-adenosylmethionine (SAMe), the primary methyl donor in the body. 
  • After donating a methyl group, SAMe becomes S-adenosylhomocysteine (SAH), which is converted back into homocysteine, completing the cycle.
MTR and MTRR

Importance of Healthy Homocysteine Levels

Homocysteine levels are significant because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High blood homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is associated with other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.

The LifeDNA Methylation Genes Report

The LifeDNA Methylation report focuses on the methylation cycle of genes to offer insights into various health and wellness aspects.

It is crucial to understand that this report does not diagnose any medical condition, substitute for professional healthcare advice, or provide medical treatment. These genetic variants are prevalent, found in 30-50% of the population, indicating their common occurrence in human DNA.

Genes Covered in the Methylation Report

  • CBS (Cystathionine Beta-Synthase): CBS converts homocysteine into cystathionine, a crucial step in the body’s process of detoxifying itself and producing glutathione, a vital antioxidant.
  • MTHFR (Methylenetetrahydrofolate Reductase): MTHFR plays a critical role in the methylation cycle by transforming a form of folate into another that is crucial for converting homocysteine into methionine, a necessary component for DNA methylation. Read our full analysis of the MTHFR gene.
  • COMT (Catechol-O-Methyltransferase): COMT helps break down neurotransmitters such as dopamine, epinephrine, and norepinephrine, regulating brain chemicals that affect mood and stress responses. Read our full analysis of the COMT gene.
  • MTR (Methionine Synthase): MTR helps complete the production of methionine from homocysteine, using a form of vitamin B12, essential for recycling homocysteine and regenerating methionine.
  • MTRR (Methionine Synthase Reductase): MTRR helps regenerate a form of vitamin B12 that MTR needs to keep producing methionine and manage homocysteine effectively.
  • MTFD1 (Methylenetetrahydrofolate Dehydrogenase 1): MTFD1 manages folate within the body and is crucial for producing certain DNA building blocks.
  • SHMT (Serine Hydroxymethyltransferase): SHMT converts serine and tetrahydrofolate into glycine and another form of folate, linking amino acid and folate metabolism.
  • VDR (Vitamin D Receptor): VDR binds with vitamin D and controls the genes’ activity in immune response and cell growth.
  • ACAT (acetyl-CoA acetyltransferase): ACAT is crucial for cellular energy production. It converts acetyl-CoA into malonyl-CoA, a key molecule in fat metabolism.
  • AHCY (Adenosylhomocysteinase): AHCY breaks down a compound into homocysteine and adenosine, crucial for maintaining the body’s methyl group balance.
  • BHMT (Betaine-Homocysteine S-Methyltransferase): BHMT helps convert homocysteine to methionine using betaine, essential for liver function and fat metabolism.
  • MAO-A (Monoamine Oxidase A): MAO-A breaks down vital neurotransmitters like serotonin and norepinephrine, helping regulate their levels in the nervous system.

NOS3 (Nitric Oxide Synthase 3): NOS3 produces nitric oxide, which helps control blood vessel dilation, blood pressure, and heart health.

How to Interpret Your Report?

To understand the report,  make a note when a variant in these genes is found,as this can indicate potential health risks or areas for improvement. Recommendations include dietary changes, lifestyle adjustments, or supplements. Always consult your healthcare professional or a genetic counselor when reviewing such reports. They can provide expert guidance on the implications of your methylation genes status and recommend personalized interventions based on your genetic makeup.

Non-Genetic Factors that Increase Your Homocysteine Levels

Watch out for these factors that contribute to higher homocysteine levels:

Dietary Changes

Lifestyle Factors

  • Smoking: Tobacco use has been shown to elevate homocysteine levels due to its negative impact on vitamin absorption and metabolism.
  • Excessive Alcohol Consumption: Drinking large amounts of alcohol can interfere with the metabolism of B vitamins, leading to higher homocysteine levels.
  • Lack of Exercise: A sedentary lifestyle can contribute to elevated homocysteine levels. Regular physical activity helps metabolize homocysteine efficiently.

Health and Medical Conditions

  • Kidney Disease: Impaired kidney function can lead to decreased clearance of homocysteine from the blood.
  • Hypothyroidism: An underactive thyroid can interfere with homocysteine metabolism, resulting in elevated levels.
  • Psoriasis: This condition can increase homocysteine levels due to increased turnover of skin cells, which raises the demand for B vitamins involved in homocysteine metabolism.

Additional Factors

  • Age and Gender: Homocysteine levels tend to increase with age and are generally higher in men compared to women.
  • Genetic Factors: Certain genetic variations, such as mutations in the MTHFR gene, can affect the metabolism of homocysteine, leading to higher levels.

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with elevated homocysteine.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids have been associated with lower homocysteine levels and improved heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

SHMT Gene And The Methylation Cycle

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SHMT Gene And The Methylation Cycle

Date of Content: May 23, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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The SHMT gene encodes the enzyme serine hydroxymethyltransferase, an enzyme essential for amino acid metabolism and nucleotide synthesis. This enzyme catalyzes the conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). This reaction is essential for various biosynthetic processes, including the methylation cycle and the synthesis of  the nucleotides, the DNA and RNA building blocks. 

The SHMT enzyme supports also the production of thymidylate and purines, which are crucial for cell division and genetic stability. It contributes to the pool of methyl groups needed for methylation reactions that regulate gene expression and protein function. Genetic variations in the SHMT gene can affect itsenzyme activity, influencing folate metabolism, homocysteine levels, and overall cellular health. These variations are associated with cardiovascular diseases, neural tube defects, and certain cancers, underscoring the gene’s importance in maintaining metabolic balance and preventing disease.

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine, a potentially harmful substance, to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. High homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine [we are here]

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine) 

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

Importance of Healthy Homocysteine Levels

Homocysteine levels are essential because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is associated with other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication can be crucial for maintaining cardiovascular health and preventing related complications.

SHMT

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine, the harmful substance, to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine [we are here]

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine)

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

SHMT Gene and the Methylation Cycle

The SHMT gene plays a critical role in the methylation cycle, a crucial biochemical pathway in DNA synthesis, repair, and gene regulation. The enzyme encoded by the SHMT gene, the serine hydroxymethyltransferase, catalyzes the conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). This reaction is integral to one-carbon metabolism, which provides the necessary methyl groups for the methylation cycle.

Role of the SHMT Gene in the Methylation Cycle

Production of 5,10-Methylenetetrahydrofolate (5,10-MTHF)

The SHMT enzyme produces 5,10-MTHF andis a crucial intermediate that sets off the methylation cycle. 5,10-MTHF is essential for synthesizing nucleotides for DNA replication and repair.

Regeneration of Methionine from Homocysteine

In the methylation cycle, homocysteine converts back to methionine using methyl groups provided by 5-methyltetrahydrofolate (5-MTHF), derived from 5,10-MTHF. This step is critical for maintaining adequate levels of methionine and S-adenosylmethionine (SAM), the body’s primary methyl donor.

Support for Methylation Reactions

SAM, produced from methionine, is used in numerous methylation reactions, including DNA methylation, which regulates gene expression, as well as the methylation of proteins and lipids. The proper functioning of the SHMT enzyme ensures a steady supply of one-carbon units needed for these reactions.

Interplay with Folate Metabolism

The SHMT gene links the folate cycle with the methylation cycle. Folate (B9), in the form of THF, is required for the SHMT enzyme to produce 5,10-MTHF. Adequate folate levels are thus necessary for the proper function of the methylation cycle and overall cellular health.

Implications of SHMT Gene Polymorphisms

The SHMT1 gene C1420T polymorphism (rs1979277 C>T/G>A), which involves a change from cytosine (C) to thymine (T) at position 1420 in the SHMT1 gene, can impact health in several ways due to its role in one-carbon metabolism and the methylation cycle. Here are the key health impacts associated with this polymorphism:

Folate Metabolism

The serine hydroxymethyltransferase enzyme, encoded by the SHMT gene, converts serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). This reaction is crucial for maintaining proper folate (B9) metabolism. The presence of the T allele at  the SHMT1 C1420T locus may influence the enzyme’s efficiency, potentially altering folate levels in the body.

Homocysteine Levels

The T-allele of the SHMT C1420T polymorphism is associated with higher homocysteine levels, which is a risk factor for cardiovascular and neurodegenerative diseases. This increase in homocysteine levels suggests that individuals with the T-allele may have a higher demand for folate to maintain normal homocysteine metabolism and prevent hyperhomocysteinemia.

Vitamin B12 Interaction

In vitamin B12 metabolism, the SHMT C1420T polymorphism may interact with other genetic factors and vitamin levels to influence health outcomes. Adequate intake of folate and vitamin B12 is essential to mitigate the potential unfavorable effects of this polymorphism.

Genotype-Specific Health Management

Individuals with the SHMT1 1420T allele (rs1979277-A) may benefit from personalized health management strategies, including dietary adjustments to ensure sufficient folate and vitamin B12 intake, regular monitoring of homocysteine levels, and preventive measures for cardiovascular and neurodegenerative diseases.

Get your LifeDNA Methylation Genes report to understand your SHMT and other methylation gene polymorphisms in detail. 

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with homocysteine levels.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids tend to lower homocysteine levels and improve heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

MTRR and MTR Genes and the Methylation Cycle

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Table of Contents

MTRR and MTR Genes and the Methylation Cycle

Date of Content: May 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article does not include all possible risk variants for the MTRR and MTR and is only for informational purposes. This article is not intended for diagnosis. Please talk to a healthcare professional if you have symptoms associated with these variants.

Why is the Methylation Cycle Important For You?

The methylation cycle is essential for numerous biological processes and overall health. Protein methylation detoxifies harmful substances, including heavy metals and toxins, thus protecting the body and supporting liver function. 

Methylation  also affects neurotransmitter production and regulation, influencing mood, cognition, and mental health. The methylation cycle helps regulate homocysteine levels, reducing the risk of cardiovascular diseases like heart disease and stroke. Furthermore, it is involved in energy production by synthesizing creatine and carnitine, both essential for metabolism and muscle function

Finally, methylation modulates the immune system, supporting the production and function of immune cells, which are crucial for combating infections and diseases. The methylation cycle is fundamental to many aspects of health and well-being.

Importance of Healthy Homocysteine Levels

Homocysteine levels are significant because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is associated with other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.

MTR and MTRR

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine, the harmful substance, to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine [we are here]

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine)

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

MTR and MTRR in the Methylation Cycle

The MTR and MTRR genes enter the methylation cycle in the third step, which is the conversion of homocysteine to methionine. Methionine is an essential amino acid that plays a crucial role in various bodily functions, including the synthesis of proteins, which are the building blocks of our cells. Methionine is also vital for SAM, a compound that helps with methylation, detoxifies harmful substances, and supports overall cell function. Foods rich in methionine include meat, fish, dairy products, nuts, and seeds.

The MTR gene  produces themethionine synthase enzyme crucial for the methylation cycle. This enzyme catalyzes the conversion of homocysteine, a potentially harmful amino acid, into methionine, an essential amino acid necessary for protein synthesis and other metabolic functions. Methionine is then converted into S-adenosylmethionine (SAM), a key methyl donor involved in numerous methylation reactions that regulate DNA synthesis, repair, and gene expression.

The MTRR gene, encodes for the methionine synthase reductase coenzyme which ensures the continuous activity of methionine synthase enzyme (encoded by the MTR gene). Methionine synthase can become inactive during the conversion of homocysteine to methionine, and methionine synthase reductase reactivates it, allowing the cycle to proceed smoothly. The MTR and MTRR genes maintain proper homocysteine levels and support the methylation cycle, which is vital for many cellular functions and overall health.

How This Can Affect You?

Polymorphisms in the MTR and MTRR genes can directly impact homocysteine levels, and  can therefore influence many health aspects.

Some studies have found that risk variants in the MTR and MTRR genes are associated with difficulties using methylcobalamin, a form of vitamin B12, and producing methionine. Methylcobalamin is a coenzyme that helps convert homocysteine to methionine. Individuals with these risk variants may have lower B12 levels because the MTR enzyme uses B12 more quickly. Vitamin B12 is crucial for DNA synthesis, cell division, red blood cell formation, energy production, mood regulation, and other essential bodily functions. Additionally, those with the risk variants may have higher homocysteine levels, particularly if their B12 levels are low, and elevated homocysteine levels have been associated with an increased risk of cardiovascular problems.

A 2007 study examined the association between MTR (A2756G, rs1805087 A>G) and MTRR (A66G, rs1801394 A>G) gene polymorphisms and levels of total homocysteine in 275 healthy women in labor who delivered full-term normal babies. Results showed that the MTR and MTRR genotypes could predict total homocysteine levels, sometimes depending on the serum folate or cobalamin levels. However, women with  MTR 2756AA had statistically significantly higher total homocysteine levels independently of the other factors. 

Get your LifeDNA Methylation Genes report to understand your MTR, MTRR and other methylation gene polymorphisms in detail. 

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with homocysteine.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids have been associated with lower homocysteine levels and improved heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

CBS Gene and its Influence on the Methylation Cycle

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Table of Contents

CBS Gene and its Influence on the Methylation Cycle

Date of Content: May 20, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article does not include all possible risk variants for the CBS gene and is for informational purposes only. This article is not intended for diagnosis. Please talk to a healthcare professional if you have symptoms associated with these variants.

What is the CBS Gene?

The CBS geneis a crucial gene encoding the enzyme Cystathionine Beta-Synthase. This enzyme plays a pivotal role in the metabolic pathway known as the transsulfuration pathway, which converts homocysteine to cystathionine. This conversion is a crucial step in metabolizing sulfur-containing amino acids. It is critical for maintaining proper levels of homocysteine and methionine in the blood.

The CBS gene is on chromosome 21. The functional pathways of the encoded enzyme, Systathionine Beta-Synthase (CBS), involves several vital biochemical processes, including cysteine, glutathione, taurine, and hydrogen sulfide synthesis. These molecules are essential for detoxification, antioxidant defense, and modulation of neurotransmission. Genetic variations in the CBS gene can lead to dysregulation of these pathways and result in elevated homocysteine levels, a condition known as hyperhomocysteinemia. This condition is associated with various health issues, including vascular diseases, neurological disorders, and congenital flaws.

The importance of the CBS enzyme extends beyond merely maintaining amino acid levels; it also impacts overall cellular health and function. Research into the role of CBS has provided insights into the complex interactions between genetics, diet, and disease. It is also a target for therapeutic interventions in diseases with sulfur metabolism disruption. For example, dietary adjustments and supplementation can help manage CBS gene mutations and their systemic effects.

Understanding the function and regulation of the CBS is crucial for comprehending broader aspects of human health and disease, particularly those related to amino acid metabolism and cardiovascular health. Ongoing research continues to reveal the intricate balance required in sulfur metabolism and the potential consequences when there is a disruption in this balance.

CBS

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine) [we are here]

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

The CBS gene produces the enzyme cystathionine beta-synthase. This enzyme uses Vitamin B6 (pyridoxine) to convert homocysteine and serine into cystathionine.

Additionally, through the transsulfuration process, cystathionine can be converted into taurine or glutathione. This process is crucial for making cysteine-containing amino acids, which are vital for protein structure, antioxidant activity, detoxification, and metabolic functions.

Importance of Healthy Homocysteine Levels

Appropriate homocysteine levels are essential because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is linked to other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.

How Does the CBS Gene Affect the Methylation Cycle?

Genetic variation in the CBS gene can influence the methylation cycle significantly due to its role in processing homocysteine, a sulfur-containing amino acid crucial for methylation reactions. 

Methylation is a biochemical process involving transferring a methyl group (one carbon atom and three hydrogen atoms) onto amino acids, proteins, enzymes, and DNA, which can affect their function and activity. The methylation cycle is vital for numerous cellular processes, including DNA repair, gene expression, and the synthesis of neurotransmitters.

Here are important functions of the CBS enzyme:

Reducing Homocysteine Levels

The enzyme encoded by the CBS gene, cystathionine beta-synthase, catalyzes the first step in the transsulfuration pathway, where homocysteine is converted into cystathionine. This conversion is crucial because it helps regulate the homocysteine level in the body. Elevated homocysteine levels can lead to a variety of health issues, including cardiovascular diseases and neurological conditions. By converting homocysteine into cystathionine, the CBS enzyme indirectly supports the recycling of homocysteine into methionine or its conversion into other sulfur-containing compounds.

Making Glutathione

Furthermore, the transsulfuration pathway facilitated by the CBS enzyme produces essential raw material for glutathione synthesis. Glutathione is a major antioxidant that protects cells from oxidative stress and helps maintain the redox balance within cells, which is crucial for normal cellular function and disease prevention.

Variations in the CBS gene can lead to altered enzyme activity, potentially causing a buildup of homocysteine and a subsequent imbalance in methylation-dependent processes. This dysregulation can impair DNA synthesis and repair, disrupt gene expression, and alter neurotransmitter synthesis, manifesting in various diseases and conditions.

Implications of the CBS Gene Variations

Several studies have looked into the role of the CBS gene variation and their effects on homocysteine levels and other health aspects.

A 2013 meta-analysis of genome-wide association studies (GWAS) involving 44,147 individuals of European descent investigated the CBS gene and 12 other loci for their association with total homocysteine (tHcy) concentrations and coronary artery disease (CAD) risk. This study aimed to determine if genetic polymorphisms linked to tHcy levels correlate with CAD. The results identified 13 loci, including six novel ones, that explained 5.9% of the variation in tHcy levels. However, a genotype risk score (GRS) based on these variants showed no significant association with CAD risk. This suggests that common genetic variants affecting tHcy levels do not influence CAD risk in white populations, thereby challenging the causal relevance of elevated tHcy levels for CAD.

A study from 2010 looked into genetic variation in the CBS gene and how this might influence susceptibility to arsenic-induced disease by affecting arsenic metabolism. In an arsenic-exposed population in Cordoba Province, Argentina, individuals with variant genotypes for CBS SNPs rs234709 and rs4920037 exhibited a 24% and 26% increase, respectively, in the proportion of arsenic excreted as the more toxic monomethylarsonic acid (%MMA) compared to wild-type homozygotes. This variation is comparable to differences observed between individuals with and without arsenic-related diseases in other studies. These findings suggest that CBS polymorphisms play a role in arsenic metabolism and potentially in the risk of arsenic-related diseases.

Get your LifeDNA Methylation Genes report to understand your methylation gene polymorphisms in detail. 

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with elevated homocysteine.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids have been associated with lower homocysteine levels and improved heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

New Study: NK-Cell Dysfunction Markers Linked To AD?

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New Study: NK-Cell Dysfunction Markers Linked To AD?

Date of Content: April 25, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article is meant for informational purposes only. LifeDNA does not offer clinical analyses nor diagnoses for any conditions discussed herein or otherwise.

The study: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1360687/full

Background

Dementia, particularly Alzheimer’s disease (AD), which constitutes 60% to 80% of cases, is becoming increasingly common due to the aging population, with projections indicating up to 152 million affected individuals by 2050

Alzheimer’s is marked by a gradual decline in cognitive functions, including memory loss, language deterioration, and changes in personality and mood, making its prevention and treatment a global challenge. There is a pressing need for biological markers that can aid in early diagnosis, differentiate between types of dementia, and predict disease outcomes. 

Aging, as the primary risk factor for AD, brings about physiological degradation and increases susceptibility to various conditions, including neurodegenerative disorders. Research suggests that aging contributes to AD through the accumulation of senescent cells which promote pathological changes by releasing inflammatory factors.

Recent advancements in the study of AD focus on the immune system’s role in its progression, particularly the involvement of Tau protein and T cells, including cytotoxic T cells observed in affected brain areas. 

Techniques like single-cell RNA sequencing (scRNA-seq) and T cell receptor (TCR) sequencing (scTCR-seq) have linked CD8 T cells to age-related AD progression. The integration of multi-omics approaches provides a comprehensive molecular insight, enhancing understanding of AD pathogenesis and helping to identify potential biomarkers. 

Furthermore, studies have shown natural killer (NK) cells play a crucial role in the immune surveillance of aging. They help mitigate inflammation, clear harmful proteins and damaged neurons, and are pivotal in managing inflammation and protein accumulation in the brain. This has led to clinical trials exploring NK cell therapies in AD patients, showing promising results in stabilizing or improving patient conditions. 

Hence, there’s an ongoing effort to delve deeper into the role of NK cells in aging and AD, leveraging biomarkers for early diagnosis and potentially curative treatments, alongside exploring the developmental trajectories of NK cells across different age groups through advanced genetic and cellular analysis.

New Study

Gaps in Alzheimer’s Genetic Research

Genetic studies on AD have provided significant insights but also face several critical gaps that hinder a fuller understanding and more effective treatment strategies. Here are some of the main gaps in current genetic studies of Alzheimer’s:

Limited Genetic Diversity

Only a few  genetic research studies on Alzheimer’s has been conducted on populations of European descent. This limits the applicability of findings to global populations, particularly given the genetic, environmental, and lifestyle variations across different racial/ethnic groups. More studies involving diverse populations are essential to uncover relevant genetic markers and risk factors specific to various ancestries.

Complex Genetic Interactions

Alzheimer’s disease is influenced by multiple genes, and the interactions between these genes can be complex. Current studies often fail to fully capture the interplay between genetic factors and how they contribute to disease risk, progression, and response to treatment.

Polygenic Risk Factors

While significant progress has been made in identifying major genes associated with Alzheimer’s, such as APOE ε4, many other genetic factors likely contribute to the disease in a polygenic manner. Other less known genes and their variants often have small individual effects that are difficult to detect with current study designs and sample sizes.

Integration with Environmental and Lifestyle Factors

There is a need for better integration of genetic data with environmental and lifestyle factors. Alzheimer’s disease is influenced by a complex interaction of genetic predispositions with factors such as diet, physical activity, exposure to toxins, and other lifestyle choices. Few studies comprehensively integrate these aspects to provide a holistic view of risk and progression.

Epigenetic Factors

Epigenetics plays a crucial role in gene expression without altering the DNA sequence. Changes in epigenetic patterns can significantly impact the development and progression of Alzheimer’s, yet this area remains underexplored compared to direct genetic studies.

Rare Variants

Current studies often focus on common genetic variants with minor effects. Rare variants might have significant impacts on disease risk and manifestation but are challenging to detect without large sample sizes or specialized study designs.

Results of the Study

NK cells, known for their dual functions in cytotoxicity and immune regulation, play a crucial role in managing infections, malignant tumors, and senescent cells (old or dying cells). 

Interestingly, while the number of these cells increases with age, their functionality declines, potentially due to decreased cytokine (protein-based immune signaling molecules) secretion and cell toxicity. This study suggests that senescent cells activate immune responses, and the NK cells respond by eliminating these cells through direct killing or secretion of cytokines.

Further, through Mendelian randomization (MR) analysis based on a cell trajectory model developed from different age groups, the study points to CHD6 as a potential gene influencing AD. CHD6, involved in DNA damage response and chromatin remodeling, is speculated to affect transcriptional activities linked to AD progression. 

How the Study Addresses Gaps in AD Research

By focusing on the role of NK cells, which increase in number but decrease in functionality with age, the study enhances the understanding of the immune system’s involvement in AD. This addresses the complex interplay between genetics and the immune system, showing how genetic predispositions can influence immune responses, potentially leading to AD progression or influencing its severity. This insight into immune-genetic interactions is crucial for developing targeted therapies that can modulate immune functions in AD.

Furthermore, the research uses advanced techniques like single-cell RNA sequencing and Mendelian randomization to investigate the role of specific genes like CHD6 in the context of AD, bridging the gap between genetic predispositions and cellular behavior. This methodological approach helps in pinpointing specific genetic pathways that contribute to AD, beyond the common genetic markers like APOE ε4. 

This studyprovides a more nuanced understanding of how aging-related genetic changes impact cellular functions and disease progression, potentially leading to the identification of new therapeutic targets and personalized treatment strategies based on an individual’s genetic and cellular profile. This aligns with the need for pharmacogenomic studies in AD, aiming to tailor treatments to genetic and cellular characteristics that may vary from one individual to another.

Possible Drawbacks of the Study

Despite the insightful findings, the study faces several limitations such as data derived solely from peripheral blood mononuclear cells. These cells may not fully represent the cellular or molecular processes occurring in other tissues, especially in diseases primarily affecting specific organs or systems, like AD.

Further, the study relied on single-cell analysis from an Asian population, and the use of GWAS data from a European cohort. 

These factors could affect the generalizability and reliability of the findings. To overcome these limitations, further studies involving larger and more diverse populations are recommended, alongside continued exploration of the underlying mechanisms and potential therapeutic targets in AD.

References

  1. https://www.who.int/news/item/07-12-2017-dementia-number-of-people-affected-to-triple-in-next-30-years#:~:text=As%20the%20global%20population%20ages,to%20152%20million%20by%202050.
  2. https://pubmed.ncbi.nlm.nih.gov/35216123/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141847/
  4. https://www.ajmc.com/view/nk-cell-therapy-snk01-improves-cognitive-function-in-alzheimer-disease-for-up-to-11-weeks
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615750/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536832/
  7. https://www.cdc.gov/genomics/disease/mendelian_randomization.htm#:~:text=Mendelian%20randomization%20can%20be%20used,%2C%20smoking%2C%20or%20alcohol%20use.

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
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Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

Understanding 23andMe’s New Historical Matches Feature

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Understanding 23andMe’s New Historical Matches Feature

Date of Content: April 24, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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23andMe has a new premium feature in their service that can reveal whether individuals are genetically related to historical figures. 23andMe’s new Historical Matches feature includes famous names such as Ludwig Van Beethoven. It also includes historically significant profiles such as a high-status Viking woman from the 9th century, an African female hunter-gatherer, or a Caquetio man from Curaçao dating back to pre-colonial times. 23andMe analyzes DNA to identify potential links between present-day individuals and their ancestors, offering insights into personal and human history. This scientific process helps individuals understand their ancestry by connecting them with past cultures and populations.

This new feature is available through its 23andMe+ Premium service. This feature allows users to identify potential genetic links to 335 historical figures by finding identical DNA segments that suggest a shared ancestor. The aim is to give users a method to trace connections to their historical lineage.

The company plans to expand the feature by adding more historical genomes. It will provide users with additional opportunities to explore their connections to history.

Dan Chu, Chief Product Officer at 23andMe, stated that “Historical Matches” represents a significant advancement in detecting genetic connections between modern individuals and historical figures. The feature uses peer-reviewed scientific methods and in-depth data analysis.

23andMe is the first prominent DNA ancestry service to offer genetic matching at this level with historical figures.

23andme's Historical Matches

How does 23andMe Match to Historical Figures?

Research by Harvard population geneticist David Reich and Svante Pääbo, a Nobel Prize winner at the Max Planck Institute for Evolutionary Anthropology, has contributed to understanding ancient human populations, migration patterns, and the relationship between Neanderthals and modern humans. Their work has challenged traditional views on human history and migration and also provided insights into disease origins that may lead to new treatments.

23andMe’s Historical Matches feature extends beyond traditional ancestry tests that trace maternal or paternal lines. This new feature scans the entire genome to find identical DNA segments that link members to historical figures who lived hundreds or even thousands of years ago.

The process uses publicly available data, scientific research, and 23andMe’s relative-matching technology to establish these connections. Like the DNA Relatives feature, Historical Matches identifies potential links by finding shared DNA segments between 23andMe+ Premium members and historical figures. The system sets quality thresholds for the length of a shared DNA segment to minimize the likelihood of incorrect matches.

Members with a 23andMe+ Premium subscription may find that they have a connection to at least one historical figure, though, per 23andMe, these connections are generally distant. In some cases, the matches may indicate closer relationships.

Which Historical Figures Are Included?

The genomes included in 23andMe’s Historical Matches feature vary widely in age; some are from individuals who lived thousands of years ago, while others date back just a few centuries. Most remain anonymous, with notable exceptions such as Ludwig van Beethoven, who passed away in 1827.

The feature provides detailed reports on each historical individual, covering aspects of their lives, how they died, and the historical context of their times, including any artifacts found with them.

Beethoven’s genetic predispositions have been explored through DNA extracted from a lock of his hair. In 2023, researchers from the University of Cambridge and the Max Planck Institute published a study analyzing Beethoven’s genome to investigate his health issues, including hearing loss, liver disease, and gastrointestinal problems.

That same year, researchers from Harvard, the Smithsonian, and 23andMe analyzed the DNA of 27 African Americans, both enslaved and freed, who worked at a Maryland iron furnace during the American Revolution and the 19th century. Published in the journal Science, the study unveils the overlooked history of these individuals. It sets the ethical and technical benchmark for studying such burial sites. Of these, the genomes of nine individuals were well-preserved, though their names are lost. The study provides insights into the harsh and often brutal conditions they endured.

Overall, the Historical Matches feature includes 335 historical figures, mostly anonymous. These individuals are grouped into different historical categories based on the original published studies, providing a narrative of their lives and times.

Which Historical Groups Are Included?

The Viking Age

During the 8th to 11th centuries, known as the Viking Age, seafaring people from Scandinavia traveled extensively, establishing settlements and trading across Europe and the North Atlantic.

Catoctin Furnace Ironworkers

The Catoctin Furnace Iron Workers consisted of enslaved and freed African American laborers who worked at one of the earliest industrial sites in the United States during the 18th and 19th centuries. This furnace produced iron goods, including artillery used during the siege of Yorktown and supplies for the Continental Army.

Iron Age Taiwan

In Taiwan, the Iron Age was when the indigenous Atayal people began utilizing metals, such as bronze, iron, and silver, for their tools and artifacts.

The Ancient Eurasian Steppe

The Eurasian Steppe is a vast expanse of grasslands extending from modern-day Hungary and Romania to Mongolia and China. It served as a significant route for human migration and played a crucial role in spreading the Indo-European languages.

The First Peoples of the Caribbean

This group includes the indigenous communities that inhabited the Caribbean region from around 1000 BC until the arrival of Spanish explorers in 1500 CE.

The Genomic Formation of South and Central Asia

Contemporary South Asian populations are primarily descendants of a mix of two ancient groups known as “Ancestral South Indians” and “Ancestral North Indians.” Ancestral South Indians emerged from an admixture of ancient Iranian farmers and southern Asian hunter-gatherers around 2000 BCE. Ancestral North Indians originated from pastoralists who inhabited the eastern Eurasian Steppe during the Bronze Age.

Late Stone Age and Iron Age South Africa

While Southern Africa is renowned for sites associated with early human ancestors dating back hundreds of thousands of years, it also has sites from more recent periods. The Late Stone Age has no definitive end date in this region. However, the Iron Age began around 200 CE with the arrival of Bantu-speaking peoples skilled in ironworking.

Ancient Northern Chinese Millet Farmers

The area between the Yellow River and the West Liao River hosted some of the world’s earliest complex agricultural societies, which cultivated millet. This cultivation and subsequent human migrations from the region helped establish millet as the staple crop of Northeast Asia nearly 8,000 years ago.

The Ancient City of Beirut

Beirut, Lebanon, has been continuously inhabited for over 5,000 years and was controlled by various empires including Assyrian, Babylonian, Persian, Greek, Roman, Byzantine, Arab, and Ottoman. Each left a cultural but not always genetic legacy.

Is the 23andMe Historical Matches Worth It?

Several users on the Reddit forum have voiced a positive opinion on this new feature. 

A user who goes by the handle ThePikminLord found the closest match with a Norse woman from Greenland, with more shared DNA than 74% of users and another with an infant girl from the Faroe Islands, with shared DNA greater than that of 71% of 23andMe users

The user Icy-You9222 reported approximately seven matches, with three from Denmark, two from Sweden, one from Estonia, and one from Ukraine. The highest percentage of shared DNA was with a young woman from Denmark, at 0.10%. As a Black American female, her Ancestry DNA results showed about 5% Swedish and Danish heritage and 1% Norwegian, while 23andMe reported 2.6% Scandinavian ancestry. She noted that these results seem consistent with her ancient Viking ancestry and expressed enjoyment in learning about her genetic background.

References

  1. https://blog.23andme.com/articles/23andmes-historic-matches
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842210/
  3. https://www.downtoearth.org.in/blog/science-technology/the-nobel-for-svante-p-bo-is-an-attempt-to-redefine-modern-man-85353
  4. https://www.cam.ac.uk/stories/beethovens-dna-reveals-health-and-family-history-clues
  5. https://hms.harvard.edu/news/historical-dna-study-connects-living-people-enslaved
  6. https://en.natmus.dk/historical-knowledge/denmark/prehistoric-period-until-1050-ad/the-viking-age/
  7. https://www.nps.gov/cato/learn/historyculture/furnace.htm
  8. https://china.usc.edu/calendar/introduction-taiwan’s-indigenous-people-and-atayal-tayan-tribe
  9. https://www.reddit.com/r/23andme/comments/1b9b9tn/my_historical_matches_i_caved_in_and_bought/
  10. https://www.reddit.com/r/23andme/comments/1b9b9tn/comment/ktvalmv/

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

LifeDNA Aging Report: A Walkthrough

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LifeDNA Aging Report: A Walkthrough

Date of Content: April 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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This is a LifeDNA Premium Report.

Aging is a natural and complex process involving gradual physiological and biological changes in an organism over time. This process affects individuals on a cellular, molecular, and organ system level. It leads to the eventual decline in physical and mental capacities and increased susceptibility towards certain conditions and  the end of an individual’s lifespan.

Biological markers of aging include:

  • deterioration of cellular functions
  • loss of telomere length
  • accumulation of metabolic waste products
  • decreased regenerative capacity of stem cells 

While aging is a universal process observed across different species, the rate and impact of aging can vary significantly due to genetic, environmental, and lifestyle factors.

LifeDNA Aging Report

How Aging Works

Aging works through several mechanisms that impact the body on a cellular and molecular level. One primary aspect is the accumulation of cellular damage over time, which includes DNA mutations and oxidative stress caused by free radicals. 

Additionally, telomeres—the protective caps at the ends of chromosomes—shorten with each cell division, leading to cellular aging and dysfunction. Hormonal changes also play a critical role, particularly the decrease in hormones like estrogen and testosterone, which affect various body systems. 

Moreover, the decline in cellular autophagy (a process by which cells clean out damaged components) and increased inflammatory responses contribute to the aging process. These changes collectively lead to the typical signs of aging, such as wrinkles, decreased mobility, and impaired cognitive functions.

LifeDNA Aging Report

The LifeDNA Aging Genetic Report analyzes genetic markers that influence the some of the aging processes and related outcomes. Here’s a general overview of the traits covered in the report and how understanding the genetics can be beneficial:

Age-related Hearing Loss

Age-related hearing loss, also known as presbycusis, is the gradual loss of hearing that occurs as people get older. This condition typically affects both ears and results from changes in the inner ear, auditory nerve, and other structures. Contributing factors include long-term exposure to loud noises, genetics, and changes in blood supply to the ear due to heart disease or high blood pressure. Hearing loss can impact speech understanding, particularly in noisy environments, and often high-pitched sounds are lost first. Genes like SIK3 have been shown to influence this trait.

Age-related Muscle Mass Loss

Age-related muscle mass loss, or sarcopenia, involves the progressive loss of skeletal muscle mass and strength beginning as early as the 30s or 40s. This decline can contribute to weakness, decreased stamina, and an increased risk of falls and fractures. Sarcopenia is driven by factors such as hormonal changes, reduced physical activity, changes in protein synthesis, muscle regeneration, and genetics. Genes like VDR and ACTN3 have been shown to be associated with this trait.

Eyelid Sagging

Eyelid sagging, in the forms of dermatochalasis or ptosis, refers to the drooping or sagging  of the upper eyelid that often occurs with age. This can be due to the weakening of the muscles that raise the eyelid (ptosis) or degeneration of the skin and soft tissue around the eyes (dermatochalasis). Eyelid sagging can impair vision if the eyelid falls low enough to cover the pupil. A 2018 GWAS identified several new genes, like MACROH2A2 (or H2AFY2), that were shown to be significantly associated with eyelid sagging.

Age-related Physical Function Impairment

Age-related physical function impairment encompasses a decline in the ability to perform daily tasks and movements effectively, such as walking, balancing, and handling objects. This impairment results from a combination of factors including muscle weakness, joint problems, neurological decline, cardiovascular limitations, and genetics. Genes like ACTN3 and UCP2 have been shown to be associated with this trait.

Risk of Repeated Falls

As people age, they face an increased risk of repeated falls due to factors such as reduced muscle strength, balance disturbances, visual impairments, and slower reaction times. Falls are a major concern in the elderly, leading to injuries like fractures and head trauma, which can significantly impair mobility and independence.  Genes like FHIT have been shown to be associated with this trait.

Vascular Aging

Vascular aging refers to the changes in the vascular system as we age, including stiffening of the arteries and reduced efficiency of blood vessels. These changes increase the risk of cardiovascular conditions such as hypertension, stroke, and heart attacks. Factors like smoking, high cholesterol, and diabetes can exacerbate vascular aging. A 2022 GWAS uncovered nearly 60 significant genes associated with this trait.

Age-related Bone Loss

Age-related bone loss, or osteoporosis, is the thinning of bone tissue and loss of bone density over time. As bones become less dense, they weaken and are more likely to fracture. This process is accelerated in women after menopause due to a drop in estrogen levels, a critical factor in bone density and health. Studies have shown that genes like ALDH7A1 significantly influence the risk for osteoporosis. The ALDH7A1 gene codes for a protein that breaks down and detoxifies acetaldehyde—a substance that disrupts the growth of osteoblasts (young bone cells) and reduces bone formation.

Age-related Cognitive Decline

Age-related cognitive decline is the gradual decrease in cognitive functioning that includes memory, thinking, and reasoning skills. While not all older adults experience significant cognitive decline, many will notice slower processing speeds and difficulties with multitasking, learning new skills, and remembering information. Studies have shown that the APOE region is significantly associated with cognitive aging. The LifeDNA Aging report covers many more such markers.

You may also like: Walkthrough of the LifeDNA Personality & Cognition Report

Age-related Muscle Weakness

Age-related muscle weakness is a decrease in muscle strength that accompanies aging and is often associated with sarcopenia. It results from a reduction in muscle fiber quantity and quality, impacting an individual’s ability to perform physical tasks and maintain independence. Genetic variation in genes like SLC39A8 have been shown to influence this trait.

Age-related Verbal Memory Decline

Age-related verbal memory decline involves the deterioration of memory functions, characterized by difficulties in recalling names, appointments, and recent events. This type of memory loss is considered a normal part of aging, distinct from the memory impairments seen in dementia and Alzheimer’s disease. A first-of-its-kind large genetic study in 2017 found significant associations between genes like APOE and memory-related parameters like immediate recall. 

Hair Graying

Hair graying is a common sign of aging caused by the gradual loss of pigment cells (melanocytes) in hair follicles. This results in hair turning gray and eventually white as pigment production decreases. Genes like IRF4 have been shown to influence this trait.

Healthy Aging

Healthy aging refers to the process of developing and maintaining the functional ability that enables well-being in older age. This concept emphasizes optimizing opportunities for physical, social, and mental health to extend life expectancy and improve the quality of life as individuals age. Factors that promote healthy aging include a balanced diet, regular physical activity, social connections, and effective management of health conditions. Genes like LRP1B have been shown to be associated with this trait.

Can Aging Be Stopped?

Currently, aging cannot be completely stopped as it is an inevitable biological process driven by complex genetic and environmental interactions. However, significant research is focused on understanding and potentially modifying the mechanisms of aging to extend the health span, the period of life spent in good health. 

While it’s unlikely that the aging process can be completely halted, interventions such as gene therapy, caloric restriction, and advanced medical treatments may potentially delay the onset of age-related diseases and extend overall lifespan. 

The field of gerontology continues to explore these possibilities, aiming to break down the biological barriers of aging.

Can Aging from Stress Be Reversed?

Aging accelerated by stress, often referred to as “stress aging,” can be partially reversed or mitigated. Chronic stress leads to increased production of cortisol, a hormone that, in high levels over prolonged periods, can have detrimental effects on the body, including accelerating aging processes. Managing stress through techniques such as mindfulness, meditation, regular physical activity, and proper sleep can significantly reduce cortisol levels. 

Furthermore, adopting a healthy diet rich in antioxidants can help repair some of the cellular damage caused by stress. While it’s challenging to completely reverse the effects of stress on aging, these lifestyle changes can improve both physical and mental health and potentially slow the aging process.

Can Aging Be Slowed Down?

Aging can be slowed down through several scientifically supported methods. Key lifestyle choices such as maintaining a balanced diet rich in fruits, vegetables, and whole grains, regular physical activity, and avoiding harmful habits like smoking and excessive alcohol consumption can significantly delay the onset of aging process with its typical signs and diseases. 

Caloric restriction has been shown in various studies to extend the lifespan of certain organisms by reducing metabolic stress. Advances in medicine, such as the use of antioxidants, hormone replacement therapies, and anti-aging skincare products, also contribute to slowing down the effects of aging.

Additionally, ongoing research into pharmacological agents that target aging processes, like senolytics which remove dysfunctional cells, holds promise for further slowing down the aging process in humans.

Why LifeDNA?

LifeDNA has emerged as a prominent option for analyzing raw DNA data from 23andMe and many other sources, owing to a combination of unique offerings and a commitment to personalized wellness. 

We offer a basic DNA data analysis package to kickstart your journey. Users with raw data from 23andMe, AncestryDNA, etc., can access close to 200 traits across interests such as Nutrition, Wellness, Vitamins and Supplements, Personality and Cognition, Fitness, Sleep, Methylation, and Skincare.

Further, if you do not have raw DNA data, such as from 23andMe, LifeDNA provides that too. Start your personalized wellness journey with LifeDNA’s state-of-the-art DNA kits here.

Here is why many regard LifeDNA as the best option for making the most of your 23andMe, AncestryDNA, and other raw data:

  • Holistic Approach to Wellness: Unlike many other platforms that focus strictly on health-related risks or ancestry, LifeDNA adopts a holistic approach. We analyze genetic data to offer personalized optimizations for nutrition (including a customized grocery list!), skin care, vitamins & supplements, wellness, personality & cognition, and fitness. This range lets users get a complete picture of their wellness needs based on their DNA.
  • Product Recommendations: We go beyond just providing insights. We offer specific product recommendations, skincare ingredients, or supplements tailored to an individual’s genetic profile. It makes our service actionable, allowing users to make immediate changes based on their results.
  • Data Security: At LifeDNA, we place a high emphasis on protecting user data. Our commitment to privacy ensures that users can trust the platform with their sensitive genetic information.
  • User-Friendly Reports: LifeDNA reports are easy to interpret. Our reports are designed to be accessible to the layperson without compromising on the depth and accuracy of the information.
  • Continual Updates: As genetic research evolves, so does LifeDNA’s platform. Users can expect their reports and insights to be updated with the latest scientific findings.
  • Dedicated Research and Development: At LifeDNA, we invest in research to continually refine our algorithms, ensuring that the insights provided are based on cutting-edge science.
  • Educational Resources: LifeDNA also provides ample resources for users to understand their genetic makeup better. This education-first approach demystifies the complex world of genetics, making it approachable and actionable for everyone.
  • Scientific Rigor: To create an unmatched commitment to scientific rigor, LifeDNA partners with CLIA-certified, CAP-accredited, and HIPAA-compliant laboratories.

References

  1. https://doi.org/10.1038/ncomms10815
  2. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182448
  3. https://doi.org/10.1038/s41467-021-20918-w
  4. https://www.nature.com/articles/mp2012159
  5. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000806
  6. https://www.frontiersin.org/articles/10.3389/fcvm.2022.1058308/full
  7. https://doi.org/10.1093/ageing/afy007
  8. https://doi.org/10.7717%2Fpeerj.980
  9. https://onlinelibrary.wiley.com/doi/10.1111/exd.13559
  10. https://doi.org/10.1002%2Fjcla.23485
  11. https://doi.org/10.1155/2017/4239648
  12. https://doi.org/10.1093/hmg/ddu346
  13. https://www.ncbi.nlm.nih.gov/books/NBK10041/
  14. https://www.genome.gov/genetics-glossary/Telomere#
  15. https://www.sciencedirect.com/topics/medicine-and-dentistry/caloric-restriction#:~:text=Caloric%20restriction%20(CR)%20is%20today,et%20al.%2C%202009).
  16. https://pubmed.ncbi.nlm.nih.gov/32686219/

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

Promethease Review: Everything You Need To Know

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Promethease Review: Everything You Need To Know

Date of Content: April 22, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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What is Promethease?

Promethease, now owned by MyHeritage, is a genetics literature retrieval system that builds a personal report based on your DNA data, primarily focused on health-related genetic variants. 

The primary appeal of Promethease lies in its affordability and comprehensive reports, backed by SNPedia, a wiki database housing a vast amount of research findings related to single nucleotide polymorphisms (SNPs).

Promethease review

What is SNPedia?

SNPedia is an online database that contains information about single nucleotide polymorphisms (SNPs), which are variations at a single position in DNA among individuals. It serves as a wiki, allowing users to contribute and edit content under the oversight of its founders. SNPedia links genetic data to medical and physiological information to help individuals understand how genetic variations may influence their health and traits. 

The website utilizes data primarily from scientific studies and public databases, providing details on how specific SNPs might be associated with health conditions, traits, or responses to drugs. It’s a valuable resource for both researchers and individuals interested in personal genomics and precision medicine.

Uploading DNA Data

Getting started with Promethease is relatively straightforward. Once you access their website, they provide a list of terms and conditions you should accept before proceeding with the tool. 

Promethease review 1

You can directly import your DNA raw data file from another company or upload it manually after paying a fee of USD 12.

Promethease review 2

Promethease accepts raw data from several providers, including 23andMe, AncestryDNA, and MyHeritage DNA.

Terms in the Report Explained

Here are some terms you might encounter in a Promethease report:

  1. SNP (Single Nucleotide Polymorphism): An SNP represents a difference in a single DNA building block called a nucleotide. SNPs occur normally throughout a person’s DNA and are the most common genetic variation among people. They can act as biological markers, helping scientists locate genes associated with any disease.
  2. Genotype: Your genotype is the specific allelic composition at a particular SNP. It represents the precise variants of a gene you have inherited. For example, at given positions in the DNA, you might have a genotype of AA, AG, or GG.
  3. Magnitude: This is a measure of how significant or impactful a finding is within the report. It is a subjective score assigned by SNPedia contributors ranging from 0 (least significant) to 10 (most significant). Higher magnitudes typically indicate findings of greater potential interest or importance.
  4. Repute: This term refers to whether a SNP is considered “Good” or “Bad.” It indicates the overall effect of the SNP according to scientific studies, whether it is a protective effect or a risk factor for a condition.
  5. Frequency: This term refers to how common a particular allele of a SNP is in the general or specific populations. It helps to understand how rare or common a genetic variation is among different groups.
  6. RSID (Reference SNP cluster ID): This is an identifier used by researchers and databases to denote a specific SNP. It helps to track and reference specific genetic variations consistently across different studies and reports.
  7. Phenotype: The term phenotype refers to observable characteristics or traits of an individual that result from the interaction of their genotype with the environment. It can include physical traits like height, eye color, and disease susceptibility.
  8. Odds Ratio: This measure is used in statistical analysis to describe the strength of association or non-independence between two data values. In the context of genetics, it represents how much a particular SNP increases or decreases the risk of a disease.
  9. Risk Allele: This is the specific gene variant version associated with an increased risk of a particular trait or disease.
  10. Protective Allele: It is a version of a gene variant that can reduce the risk of a particular trait or disease.

These terms are used within Promethease reports to provide detailed insights into your genetic make-up, and how it might influence various health-related traits and conditions. Understanding these terms can help you better interpret the results of your genetic analysis.

Turn-Around-Time

It may take up to 24  hours for Promethease to generate the report, depending on the server load. 

Upon receiving the email that the report is ready, you can navigate the website and immerse yourself in a wealth of information. The report has numerous sections on various conditions, traits, and medications.

Each genetic variant in the report is presented with a magnitude score, indicating the importance of that particular SNP variant. 

Furthermore, it indicates whether the variant is good or bad and its frequency within the population.

The Promethease Report

One of the first impressions of the Promethease report is its sheer volume of data. It can feel overwhelming if you are new to genetics.

Promethease report is text-based with limited visuals, which can be challenging to read for the uninitiated. 

The report also uses scientific language and jargon like SNP, allele, genotype, or rsID. If unfamiliar with these terms, you might frequently need to refer to external resources to understand the report fully.

Accuracy and Interpretation

Promethease pulls data from SNPedia. However, it is crucial to remember that interpreting genetic data, especially in the context of health, is complex. 

The presence of a particular SNP allele might increase the risk of a condition, but it doesn’t guarantee you’ll get it. Many factors, including other genes and environment, come into play.

Promethease emphasizes that its report is not a diagnosis and that customers should discuss concerning findings with a healthcare professional. 

Can Family Tree DNA (FTDNA) data be Uploaded to Promethease?

Family Tree DNA (FTDNA) allows users to download their raw DNA data, which they can upload to a third-party tool like Promethease for additional analysis. 

This raw data includes results from FTDNA’s Family Finder (autosomal DNA), Y-DNA, and mtDNA tests.

However, it’s important to note that Promethease is designed to interpret autosomal data related to health and traits. 

While you can technically upload Y-DNA and mtDNA data to the site, the interpretations for these data are limited, as they are not the primary focus of the Promethease database.

It is also essential to check the terms and conditions and privacy policies of any third-party tools you consider using, as using such services can often have implications for your genetic data privacy.

For the most current and detailed instructions, please visit the respective websites of Family Tree DNA and Promethease.

Promethease Privacy Policy

Promethease claims not to share, sell, or utilize your genetic data after creating the report. 

As of December 2019, after being acquired by MyHeritage, Promethease implemented a policy of deleting all DNA data files within 30 days of upload.

Is Promethease worth it?

  1. Affordability: Promethease is more affordable than similar services, making it accessible to many users.
  2. Comprehensive Data: The platform provides detailed genetic reports based on SNPs. It offers a rich source of information for individuals interested in their genetic predispositions.
  3. Data from SNPedia: Promethease uses data from SNPedia, a respected, peer-reviewed resource, which adds credibility to their reports.
  4. Privacy Focused: Promethease deletes user data within 30 days of upload, reflecting its commitment to privacy.

Accepts Data from Multiple Providers: Promethease accepts raw DNA data from many major DNA testing companies, making it a versatile choice for analysis.

Cons of using Promethease

  1. Overwhelming Information: The bulk of information provided can be overwhelming, especially for users with little to no background in genetics.
  2. Complex Terminology: Using scientific and technical language can make the reports hard to understand for laypersons.
  3. Lack of Visuals: The reports are text-based with minimal visual aids, which may detract from user experience and comprehension.
  4. Time to Generate Reports: The report can take several hours to generate, which may be inconvenient for some users.
  5. Not a Diagnostic Tool: While it provides risk estimates based on genetic variants, Promethease is not a diagnostic tool. Some users might misunderstand the nature of the information provided, leading to unnecessary worry or inappropriate health decisions.

Alternative to Promethease: Why LifeDNA?

LifeDNA has emerged as a prominent option for analyzing raw DNA data from 23andMe and many other sources, owing to a combination of unique offerings and a commitment to personalized wellness. 

We offer a basic DNA data analysis package to kickstart your journey. Users with raw data from 23andMe, AncestryDNA, etc., can access close to 200 traits across interests such as Nutrition, Wellness, Vitamins and Supplements, Personality, Fitness, Sleep, Methylation, and Skincare.

Further, if you do not have raw DNA data, such as from 23andMe, LifeDNA provides that too. Start your personalized wellness journey with LifeDNA’s state-of-the-art DNA kits here.

Here is why many regard LifeDNA as the best option for making the most of your 23andMe, AncestryDNA, and other raw DNA data:

  • Holistic Approach to Wellness: Unlike many other platforms that focus strictly on health-related risks or ancestry, LifeDNA adopts a holistic approach. We analyze genetic data to offer personalized optimizations for nutrition (including a customized grocery list!), skin care, vitamins & supplements, wellness, personality & cognition, and fitness. This range lets users get a complete picture of their wellness needs based on their DNA.
  • Product Recommendations: We go beyond just providing insights. We offer specific product recommendations, skincare ingredients, or supplements tailored to an individual’s genetic profile. It makes our service actionable, allowing users to make immediate changes based on their results.
  • Data Security: At LifeDNA, we place a high emphasis on protecting user data. Our commitment to privacy ensures that users can trust the platform with their sensitive genetic information.
  • User-Friendly Reports: LifeDNA reports are easy to interpret. Our reports are designed to be accessible to the layperson without compromising on the depth and accuracy of the information.
  • Continual Updates: As genetic research evolves, so does LifeDNA’s platform. Users can expect their reports and insights to be updated with the latest scientific findings.
  • Dedicated Research and Development: At LifeDNA, we invest in research to continually refine our algorithms, ensuring that the insights provided are based on cutting-edge science.
  • Educational Resources: LifeDNA also provides ample resources for users to understand their genetic makeup better. This education-first approach demystifies the complex world of genetics, making it approachable and actionable for everyone.
  • Scientific Rigor: To create an unmatched commitment to scientific rigor, LifeDNA partners with CLIA-certified, CAP-accredited, and HIPAA-compliant laboratories.

References

  1. https://promethease.com/
  2. https://www.snpedia.com/

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

Understanding The APOE Gene Part I: The Basics

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Understanding The APOE Gene Part I: The Basics

Date of Content: March 19, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article is meant for informational purposes only. LifeDNA does not offer clinical analyses nor diagnoses for any conditions discussed herein or otherwise.

A few genes and their variants stand out for their profound impact on our health in the intricate web of human genetics.  The APOE (apolipoprotein E) gene is one such gene, commanding attention for its significant role in lipid metabolism and its association with various conditions. 

The APOE gene is located on chromosome 19. It is best known for its involvement in the body’s ability to process fats and for influencing conditions ranging from cardiovascular disease, affecting the functioning of the heart, to Alzheimer’s disease. The importance of the APOE gene in medical research and personalized healthcare continues to grow as we uncover more about its diverse roles in the body. 

This article delves into the APOE gene, exploring its biological functions, genetic variations, and the implications of these variations on health and disease. By understanding the APOE gene, we can better grasp the complexities of genetic influence on health and pave the way for more personalized medical interventions.

APOE gene

The Biology of APOE

The APOE gene provides instructions for making a protein called apolipoprotein E. This protein is crucial for the normal catabolism (breakdown) of triglyceride-rich lipoprotein constituents. 

In simpler terms, it plays a vital role in metabolizing and transporting fats and cholesterol throughout the body, aiding in the clearance of these substances from the bloodstream

Apolipoprotein E is a prominent component of very low-density lipoproteins (VLDL), which are precursors to the more well-known low-density lipoprotein (LDL), often referred to as “bad cholesterol.”

Read more: How Genes Influence Cholesterol Levels.

Beyond its role in lipid metabolism, APOE plays vital roles in several other biological processes, including immune regulation and neural repair. Its presence in different tissues and organs, notably the liver and brain, underscores its multifaceted role in maintaining health and its potential implications in disease processes.

Genetic Variations of APOE and Their Significance

The APOE gene exists in three principal allele forms: ε2, ε3, and ε4, creating a genetic variant that influences the protein’s structure and function. These alleles determine the individual’s APOE genotype, which can be combinations of the three alleles (e.g., ε3/ε3, ε3/ε4, ε4/ε4).

  • ε2 allele is the least common. It is associated with a decreased risk of Alzheimer’s but an increased risk of type III hyperlipoproteinemia (a condition that can lead to cardiovascular disease).
  • ε3 allele is the most common, considered the “neutral” allele, with no increased risk of Alzheimer’s or heart disease.
  • ε4 allele is associated with an increased risk of Alzheimer’s disease and cardiovascular diseases. Carrying even one ε4 allele increases the risk, and having two ε4 alleles further elevates this risk.

The distribution of these alleles varies widely across different populations and ethnic groups, affecting the prevalence of related diseases. Understanding one’s APOE genotype can offer insights into the potential health risks and the preventive measures that may be most effective.We will cover the population-specific influence of APOE in Part II.

APOE and Its Link to Diseases

The APOE gene’s association with various diseases, most notably Alzheimer’s disease and cardiovascular disease, underscores its importance in human health and disease. The link between APOE alleles and these conditions offers a window into the genetic underpinnings of disease risk and progression.

Alzheimer’s Disease (AD)

The ε4 allele of the APOE gene is the strongest-known genetic risk factor for late-onset Alzheimer’s disease, expressed in more than half of the affected patients. Individuals carrying one ε4 allele have an increased risk of developing the disease, and the risk is even higher for those with two ε4 alleles. The presence of the ε4 allele is associated with earlier onset of AD symptoms and a more rapid progression of the disease. 

In a study examining 179 senile dementia of the Alzheimer type (SDAT) patients, 154 controls, and 167 subjects with age-related memory complaints (ARMC), it was found that the APOE-ε4 allele frequency was notably higher in SDAT patients (27%) compared to controls (10%) and stable ARMC subjects (15%). Furthermore, among ARMC subjects, those who carried the ε4 allele had a three-fold increased risk of developing dementia compared to non-carriers. Additionally, older age at the onset of memory decline and lower initial scores were also associated with an increased risk of dementia in ARMC subjects.

Two years ago popular Marvel star Chris Hemsworth discovered that he had two copies of the APOE4 gene, inherited from both his mother and father. You can read about his journey of discovery here.

Conversely, the ε2 allele may offer some protection against AD, although its protective mechanism is not fully understood.

A 2020 study revealed significant protective effects of ε2 against AD-related pathologies such as amyloid plaques and Braak stage compared to e3/e3 carriers and e4 carriers. The study also noted that, unfortunately, in ε2/ε4 carriers, the risk for AD pathologies resembles that of ε4 carriers rather than ε2 carriers. 

Cardiovascular Disease (CVD)

An early study suggested that the presence of ε2 or ε4 alleles in men is associated with a heightened risk of CVD, emphasizing the potential utility of genotype information in identifying individuals prone to CVD events.

In addition to the increased risk for AD, the APOE ε4 allele is also associated with an increased risk of cardiovascular disease. This risk is partly due to the allele’s effect on lipid metabolism, leading to higher LDL cholesterol levels and potentially a significant buildup of plaques in the arteries. 

The ε2 allele, despite its protective role against Alzheimer’s, can predispose individuals to type III hyperlipoproteinemia, a condition that elevates triglyceride levels and may increase the risk of heart disease.

Beyond these well-established links, research has suggested potential associations between APOE alleles and other conditions, including diabetes, inflammatory diseases, and age-related macular degeneration, highlighting the gene’s broad impact on health.

Implications for Personalized Medicine

Understanding an individual’s APOE genotype has significant implications for personalized medicine, offering insights that can guide preventive health strategies, lifestyle adjustments, and potentially tailored medical treatments.

  • Preventive Health Strategies: Knowledge of one’s APOE status can inform personalized approaches to disease prevention. For instance, individuals with the ε4 allele might benefit from early interventions to manage cholesterol levels and reduce Alzheimer’s risk, such as regular physical activity, a heart-healthy diet, and cognitive training exercises.
  • Lifestyle Adjustments: Awareness of APOE-related risks can motivate lifestyle changes to mitigate these risks. It could include dietary modifications, increased emphasis on cardiovascular exercise, and monitoring heart health and cognitive function regularly.
  • Tailored Medical Treatments: In the future, the APOE genotype could inform the development and application of targeted therapies, especially for conditions like Alzheimer’s, where we can customize preventive and therapeutic strategies based on genetic risk factors.

Future Directions in APOE Research

Ongoing research into the APOE gene continues to uncover its complex roles in health and disease. Future studies aim to elucidate mechanisms by which APOE alleles influence disease risk and progression to develop more effective treatments. Research also explores the gene’s potential roles in other conditions, expanding our understanding of its impact on human health.

Takeaway

The APOE gene’s significance extends far beyond its role in lipid metabolism, with its variants influencing the risk and progression of Alzheimer’s disease, cardiovascular disease, and potentially other conditions. Understanding the genetic variations of APOE and their associations with diseases offers valuable insights for personalized medicine, highlighting the importance of genetics in health and disease management. 

As research progresses, the potential for targeted interventions based on APOE status holds promise for improving outcomes for individuals with increased genetic risks. Embracing the advancements in genetic research can empower individuals and healthcare providers to make informed decisions, leading to better health and well-being.

Other Gene-Related Articles Covered By LifeDNA

MTHFR

The MTHFR gene, short for Methylenetetrahydrofolate Reductase, is crucial in the body’s metabolic processes. This gene produces the MTHFR enzyme, which plays a vital role in processing amino acids, the building blocks of all proteins

Read our complete review of this gene here: Decoding The MTHFR Gene & What It Means For Your Wellness

COMT

The COMT enzyme, encoded by the COMT gene, is particularly active in the prefrontal cortex, a brain region associated with memory, decision-making, and emotional regulation. Genetic variations in the COMT gene can affect the enzyme’s activity level, influencing how quickly catecholamines are metabolized. This can directly impact neurological and psychological processes.

Read our complete review of this gene here: COMT Gene Insights: Navigating Its Influence On Wellness

References

  1. https://medlineplus.gov/genetics/gene/apoe/
  2. https://www.sciencedirect.com/science/article/abs/pii/S1552526014024996
  3. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1468-1331.1996.tb00266.x
  4. https://link.springer.com/article/10.1186/s13024-022-00574-4
  5. https://www.nature.com/articles/s41467-020-18198-x
  6. https://www.sciencedirect.com/science/article/abs/pii/S0021915000005700
  7. https://link.springer.com/article/10.1186/s13024-022-00574-4

Alternative to Affinity DNA: Why LifeDNA?

LifeDNA has emerged as a prominent option for analyzing existing DNA data from 23andMe and many other raw data sources in addition to offering our own proprietary sample collection kits. Our reports feature a combination of unique offerings and a commitment to personalized wellness. 

We offer a basic DNA raw data analysis package to kickstart your journey. Users with raw data from 23andMe, AncestryDNA, etc., can access 194+ traits across interest areas such as Nutrition, Wellness, Vitamins and Supplements, Personality, Fitness, Sleep, Methylation, and Skincare.

Further, if you do not have raw DNA data, such as from 23andMe, LifeDNA provides that too. Start your personalized wellness journey with LifeDNA’s state-of-the-art DNA kits here.

Here is why many regard LifeDNA as the best option for making the most of your 23andMe, AncestryDNA, and other raw data:

  • Holistic Approach to Wellness: Unlike many other platforms that focus strictly on health-related risks or ancestry, LifeDNA adopts a holistic approach. We analyze genetic data to offer personalized optimizations for nutrition (including a customized grocery list!), skin care, vitamins & supplements, wellness, personality & cognition, and fitness. This range lets users get a complete picture of their wellness needs based on their DNA.
  • Product Recommendations: We go beyond just providing insights. We offer specific product recommendations, skincare ingredients, or supplements tailored to an individual’s genetic profile. It makes our service actionable, allowing users to make immediate changes based on their results.
  • Data Security: At LifeDNA, we place a high emphasis on protecting user data. Our commitment to privacy ensures that users can trust the platform with their sensitive genetic information.
  • User-Friendly Reports: LifeDNA reports are easy to interpret. Our reports are designed to be accessible to the layperson without compromising on the depth and accuracy of the information.
  • Continual Updates: As genetic research evolves, so does LifeDNA’s platform. Users can expect their reports and insights to be updated with the latest scientific findings.
  • Dedicated Research and Development: At LifeDNA, we invest in research to continually refine our algorithms, ensuring that the insights provided are based on cutting-edge science.
  • Educational Resources: LifeDNA also provides ample resources for users to understand their genetic makeup better. This education-first approach demystifies the complex world of genetics, making it approachable and actionable for everyone.
  • Scientific rigor: To create an unmatched commitment to scientific rigor, LifeDNA partners with CLIA-certified, CAP-accredited, and HIPAA-compliant laboratories.

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports and suggestions do not diagnose or treat any health conditions or provide any medical advice. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results.