MTHFR: How to check your data for C677T and A1298C

It is easy to check your genetic results on 23andMe or AncestryDNA for the two main MTHFR variants known as C677T and A1298C.  You don’t need to do a separate MTHFR test, nor do you need the health reports to access this data.

This article will show you how to check your raw data, and then it explains the scientific research on the MTHFR variants. There is a lot of misinformation on the internet about the MTHFR gene mutations.  I’m going to stick with the peer-reviewed research studies here.

MTHFR Gene Mutation: Check your raw data

  • If you have 23andMe data, log in on 23andMe.com and go to “browse raw data”.  Cut and paste the rs id (e.g. rs1801133) to see your genotype.
  • If you have AncestryDNAresults, you will need to download your raw data file and search for the rs id number below. (How to download AncestryDNA and Search)
  • Or…  become a Member and see your data right in all Genetic Lifehacks articles.

Members: Log in to see your data below.

Check your genetic data for rs1801133 (23andMe v4, v5; AncestryDNA):

  • G/G: typical *
  • A/G: one copy of MTHFR C677T allele, enzyme function decreased by 40%
  • A/A: two copies of MTHFR C677T, enzyme function decreased by 70 – 80%

Members: Your genotype for rs1801133 is .

Check your genetic data for rs1801131 (23andMe v4, v5; AncestryDNA):

  • T/T: typical *
  • G/T: one copy of MTHFR A1298C (heterozygous), slightly decreased enzyme function
  • G/G: two copies of MTHFR A1298C (homozygous), decreased enzyme by about 20%

Members: Your genotype for rs1801131 is .

 

Let’s dig into the details on what “MTHFR” is and what the research shows about these variants.


What is the MTHFR gene?

The MTHFR gene codes for an enzyme that is an important part of the methylation cycle. The enzyme is called “methylenetetrahydrofolate reductase” or MTHFR (same as the gene).

There is a lot of swirl about MTHFR — with people thinking the “MTHFR mutation” is the cause of everything under the sun. This seems to have caused a backlash, with doctors claiming that MTHFR variants are completely unimportant.

Let’s cut through the hype, and I’ll explain the science.

Essentially, research shows that the MTHFR variants statistically increase the risk of quite a few health issues.. But this relative risk needs to be kept in perspective and considered along with environmental factors (diet, lifestyle, etc.).

At the end of the article, you will find solid, evidence-based, lifestyle solutions for optimizing for the MTHFR variants.

What is the methylation cycle?

I mentioned above that the MTHFR gene codes for an enzyme that is an important part of the methylation cycle.

Methylation is the adding and removing of a methyl group (CH3) to amino acids, DNA, and other enzymes or proteins.

Most of the molecules in our body are chains of hydrocarbons — carbons plus hydrogens. So adding a methyl group stacks on one more link in a hydrocarbon chain. Sometimes it helps me to visualize it as the molecule being made of Legos, and the methyl group is just adding another Lego component onto your creation.

Adding a methyl group – or an extra carbon plus three hydrogens – then changes the original molecule into something different.

Here’s an example:
A methyl group is added to the neurotransmitter serotonin in the conversion to melatonin.

 

That little methyl group is also important when it comes to your DNA in the cell nucleus. By binding to certain spots on a chromosome, methylation can turn on and off genes, maintain and repair your DNA, and alter proteins.

Methylation is important in the nervous system, in the production and breakdown of neurotransmitters, and in the detoxification of some environmental toxicants.

The methylation cycle also intimately involves heart health. It controls the level of homocysteine, an important marker of heart disease risk. It is also involved in cholesterol levels.[ref ]  Genetic variants in the methylation pathway have been linked to heart disease in many studies.

Additionally, the pathway involves the regulation of hormones, such as estrogen, as well as playing a role in histamine levels.

Optimizing your methylation cycle can balance out a lot of health issues, so read on to find out more as well as specific solutions for the MTHFR C677T and A1298C variants…

What does the MTHFR enzyme do?

MTHFR is a central gene in the methylation cycle and is a limiting factor for producing methyl groups from folate. Common genetic variants in the coding of this gene affect more than half the population.

Specifically, the MTHFR (methylenetetrahydrofolate reductase) gene codes for an enzyme that turns folate into the active form, 5-methyltetrahydrofolate, that your body uses. This, along with the active form of vitamin B-12  (methylcobalamin), drives an important portion of the methylation cycle.

Here is an image to explain:

 

Recap: MTHFR codes for an enzyme in the methylation cycle. The methylation cycle affects detoxification, neurotransmitters (mood), hormones, and much more. Optimizing your methylation cycle can have many overall health benefits.

What do MTHFR C677T and A1298C  mean?

Let’s talk about terminology…

  • A mutation is a change in a gene that happens in less than 1% of the population. These are the rare changes.
  • A polymorphism is a change that occurs in the gene for more than 1% of the population. We all have lots of different polymorphisms — these are the small changes that make us all unique.

The MTHFR C677T variant is considered a single nucleotide polymorphism(SNP) meaning one nucleotide base pair (the As, Cs, Gs, and Ts) is different for part of the population.

Neither MTHFR C677T nor A1298C variants are considered mutations because both are commonly found in the population.

 

What problems can the MTHFR C677T or A1298C variants cause?

The MTHFR gene is one of the most well-researched genes, with over 6,000 studies investigating the C677T variant.

Research shows that the MTHFR genetic variants (C677T and A1298C) have links to a statistically increased relative risk of:

Carrying an MTHFR variant statistically associates with an increase in the risk of the above diseases (and many others), but this does not mean that it will cause you to have that disease. It just increases susceptibility to diseases when diet and lifestyle factors are not optimal.

More importantly, food choices or supplemental methyl folate can eliminate the problems from the MTHFR variants.

Getting specific on the MTHFR C677T variant:

The MTHFR variants cause a reduction in methyl folate levels.

The MTHFR C677T is a change in one nucleotide base at one spot in the gene. The variant slightly changes the protein structure. This change causes the enzyme to break down faster at normal body temperature, thus reducing the amount of enzyme available.[ref][ref][ref]

People with the rs1801133 A/A genotype have the greatest impact. They have about a 70% reduction in enzyme function.

Why do some doctors think that MTHFR variants are not important?

The very extensive research (it’s one of the most researched genes) shows MTHFR variants have links to an increased relative risk for the disorders listed above, as well as a bunch of other diseases.

While an MTHFR variant can play a role in susceptibility to many different chronic diseases, it usually isn’t the absolute cause for most diseases. Instead, it’s just one part of the picture.

When patients flood into the doctor’s office to demand treatment for ”having the MTHFR gene”, the automatic backlash is to say that MTHFR variants aren’t important. (Terminology pet peeve – everyone has the MTHFR gene! It’s one of those genes you can’t live without.)

Most physicians are trained to treat diseases (or the symptoms of a disease) rather than hunting down all of the various aspects of lifestyle, diet, and environment that could be contributing to the disease. They simply don’t have the time in a 10-minute visit to discuss the nuances of diet, genetics, toxicant exposure, etc. To be fair, most people going to a doctor with an ailment expect to get a simple answer or pill that solves the problem immediately.

Does the MTHFR variant increase the risk of heart disease?

There are extensive studies showing a link between MTHFR C677T and an increased risk of cardiovascular disease. A meta-study that combined other study results shows that the MTHFR 677 A/A genotype increases the relative risk of heart disease by 38%.[ref] With heart disease being the number one killer in most countries, a 38% increase in risk is important.

Overall, optimizing your methylation cycle can be important to your health (especially heart health). It is definitely a foundational first step!

Are there more than just the MTHFR C677T and A1298C variants?

While the C677T and A1298C variants are the most well studied, there are several other genetic variants in the MTHFR gene.  If you are a Genetic Lifehacks member, read through the article Beyond MTHFR C677T for several other variants that also have a significant impact on gene function.


Lifehacks: Actions you can take with MTHFR

Knowing that you carry an MTHFR genetic variant can help guide your choice of foods and supplements. Through optimizing your diet, you can mitigate the risks from the MTHFR variants.[ref]

Diet for MTHFR:

Increase folate-rich foods:
Increasing your intake of folate from foods will help mitigate some of the risks from the MTHFR variant. Foods containing lots of folate include leafy greens, lentils, liver, asparagus, liver, and broccoli.

A recent study showed that increasing folate-rich foods is enough to reduce homocysteine levels as well as inflammatory markers in women with the MTHFR C677T variant. The study showed that eating 191 ug of folate from vegetables each day caused a significant change.[ref]

Need more information? Check out Folate-rich foods and recipes for MTHFR

Folate is not exactly folic acid…
Note that when you are looking at folate content, you need to make sure the ingredients list isn’t referring to folic acid (a synthetic form found in processed foods). Not everyone processes folic acid the same way.

Related article: Folic acid and your genes

Increase your choline intake: 
Choline can help your body bypass a lack of folate in the methylation cycle.[ref ][ref ]

Good sources of choline include egg yolks, beef liver, and wheat germ.

A metabolite of choline, betaine, is what works through the methylation cycle; therefore, food sources of betaine (beets, quinoa, and spinach) are also helpful here. Supplemental betaine (also called TMG) is also available.  (People with two copies of the slow COMT variant may want to be careful with supplementing with TMG.)

Related article: Choline-rich foods and recipe ideas

MTHFR Supplements:

If your diet isn’t providing enough of the nutrients needed in the methylation cycle, you may want to consider supplements to increase your intake.  Alternatively, you could experiment with supplements on a short-term basis to see exactly which nutrients you need to include more of in your diet.

Supplemental Methyl Folate and B12:

  • If you aren’t getting enough folate from foods, you could try a low-dose methyl folate supplement.
  • Vitamin B12 is also important in the methylation cycle, so you need to ensure you are getting enough B12 either through diet (animal-based foods) or supplements.

Note: People who have the slow COMT genetic variant may want to be careful about high-dose supplements that affect the methylation cycle, such as methyl folate and methylB12. Instead, stick with dietary folate and use alternative forms of B12 such as adenosyl and hydroxocobalamin. Read all about COMT and supplement interactions.

Riboflavin (vitamin B2):
The MTHFR C677T variant decreases its ability to bind to FAD, a riboflavin-dependent enzyme.[ref] If you have high homocysteine (a marker for heart disease risk), studies show that adding riboflavin lowers homocysteine levels in those with the A/A genotype.[ref][ref] Other research points to riboflavin decreasing homocysteine levels only if vitamin B6 levels are adequate.[ref]

Creatine and MTHFR:
The creation of creatine in the body consumes about 40% of the methyl groups created in the methylation cycle.[ref]  Creatine supplementation has been shown in trials to decrease homocysteine levels.[ref]

Check your homocysteine levels:

High homocysteine levels increase the risk of heart disease.  Methyl folate plus B12 and B6 may help reduce your homocysteine.[ref ]

Ask your doctor about getting your homocysteine checked the next time you or there for a physical.  Alternatively, in the US, you can order this test online without a trip to the doctor through UltaLabs for $34  (*affiliate link) or other online testing providers.


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Related Articles and Genes:

High Histamine and Methylation (MTHFR variants)
Histamine is a molecule that plays many roles in the body. It is involved in allergic reactions, plays a role in our immune defense system, acts as a vasodilator, and is a neurotransmitter. While most of us think of histamine only when reaching for an antihistamine during allergy season, it is a vital part of our body’s everyday functions.

COMT – Genetic Connections to Neurotransmitter Levels
Having trouble with supplements containing methyl groups? Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. This important enzyme is tasked with breaking down neurotransmitters, such as dopamine.

MTHFR and Vaccinations
You may have read or heard that anyone who carries MTHFR variants should not be vaccinated. Usually, the reason given is that those with decreased MTHFR enzyme activity cannot detoxify or ‘handle’ vaccinations, often with references to mercury in the vaccines. This article reviews the published scientific studies on the topic of MTHFR and vaccinations.

MTHFR Polymorphisms – Beyond 677
If you are just getting started with researching your MTHFR polymorphisms, you may want to start with some background information. I have a list of resources on the MTHFR page that you might find helpful. MTHFR is a key gene in regulating the body’s folate metabolism and, consequently, is involved in the methylation cycle.

MTR and MTRR Variants
MTR (methionine synthase) and MTRR (methionine synthase reductase) are two genes involved in the conversion of homocysteine to methionine, and a couple of fairly common gene variants cause the genes to work differently.

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