Understanding 23andMe MTHFR Gene Variants & Mutations

What Is MTHFR?

MTHFR is an abbreviation for methylenetetrahydrofolate reductase, which serves a dual purpose.

It refers both to a critical enzyme in the human body and to the gene that carries the instructions for making that enzyme.

The MTHFR enzyme is also instrumental in the conversion of dietary folate and folic acid into their active form, 5-methyltetrahydrofolate, which is used in a number of critical bodily functions.

Folate metabolism is necessary for DNA synthesis and repair, cellular division, amino acid synthesis, and the formation of red and white blood cells.

The term “MTHFR” is also used to refer to the gene that provides the instructions for making the MTHFR enzyme.

This gene is located on chromosome 1 at location 1p36.3.

Certain genetic variants or mutations in the MTHFR gene can lead to reduced activity of the enzyme, which can in turn lead to elevated levels of homocysteine in the blood (hyperhomocysteinemia), especially when the diet is low in folate.

Elevated homocysteine levels are associated with an increased risk of cardiovascular disease, venous thrombosis, certain types of cancer, and other health issues.

In addition, because the MTHFR enzyme is involved in folate metabolism, mutations in the MTHFR gene can affect levels of folate in the body and can potentially contribute to neural tube defects in developing embryos, certain psychiatric disorders, and other health conditions.

However, it’s important to note that having a mutation in the MTHFR gene does not guarantee the development of health problems.

Many people with MTHFR mutations do not develop any health issues, and the potential impact of these mutations is influenced by other genetic and lifestyle factors.

MTHFR is vital for a variety of bodily functions, including:

DNA synthesis and repair

Methylation helps regulate the synthesis and repair of DNA, playing a vital role in human growth and development.

Regulating gene expression

By adding a methyl group to the DNA molecule, methylation can change the activity of a DNA segment without changing its sequence, influencing the production of proteins and enzymes.

Processing amino acids

A key role of the MTHFR enzyme is to help convert the amino acid homocysteine into another amino acid, methionine, which the body uses for protein synthesis and other critical tasks.

Metabolizing folate

The MTHFR enzyme also converts the form of folate obtained from the diet into the active form of folate (5-MTHF, or 5-methyltetrahydrofolate) that can be used by the body. Folate, also known as vitamin B9, is essential for many body functions, including cell division and the synthesis of DNA and amino acids.

If the MTHFR gene has certain mutations or variants, it can result in an MTHFR enzyme that is less efficient, which can disrupt these processes and potentially lead to a variety of health problems.

**What Is An MTHFR Test?**

An MTHFR test is a type of genetic test that checks for mutations in the MTHFR gene. This gene provides the instructions for making the MTHFR enzyme. If a person has certain mutations in this gene, it can result in a poorly functioning MTHFR enzyme. The two most commonly studied MTHFR gene mutations are known as C677T and A1298C.

This test is typically performed with a blood sample, though it can also be done with a saliva sample. The sample is sent to a lab where technicians look for specific mutations in the MTHFR gene.

23andMe MTHFR Gene Variants in the Raw Data

23andMe is a direct-to-consumer genetic testing service that provides raw genetic data, which can be used to assess different genetic traits, ancestry, and potential health risks.

While 23andMe does test for a wide variety of genetic variants, it’s important to note that the service doesn’t cover all possible genetic variants and isn’t meant to be a diagnostic tool.

23andMe does include data for some MTHFR gene variants in their raw data.

However, it may not provide interpretations for these variants.

To find specific MTHFR variants in your 23andMe raw data, you would need to know the specific SNP (Single Nucleotide Polymorphism) identifiers associated with MTHFR.

Here are the two most common MTHFR gene mutations and their corresponding rs numbers, which are the identifiers used by databases to refer to specific genetic variants:

C677T: The rs number is rs1801133. For this variant, the T allele is the variant allele.
A1298C: The rs number is rs1801131. For this variant, the G allele is the variant allele.

Once you’ve located these rs numbers in your 23andMe raw data, you can see which alleles you have at these locations.

The ACTGenes MTHFR DNA Raw Data Analysis report provides you a detailed analysis of your MTHFR gene variants

However, understanding what these variants might mean for your health can be complex and is best done in consultation with a healthcare provider or a genetic counselor.

DISCLAIMER: It’s important to remember that having a variant in the MTHFR gene isn’t a guarantee of health issues. Many people with MTHFR mutations are healthy, and the impact of these mutations can be influenced by other genetic and lifestyle factors.

Here’s an example of an SNP table for MTHFR genetic variants with rs identifiers, alleles, and implications:

SNP	Risk Allele	Possible Genotypes	Implication
rs1801133	T	CC, CT, TT	This SNP corresponds to the C677T mutation in the MTHFR gene. The T allele represents the variant. Having one T allele (CT) is associated with a slightly decreased MTHFR enzyme activity. Having two T alleles (TT) is associated with a more significant decrease in MTHFR enzyme activity, potentially leading to elevated homocysteine levels, especially if dietary folate intake is low.
rs1801131	G	AA, AG, GG	This SNP corresponds to the A1298C mutation in the MTHFR gene. The G allele represents the variant. The AG and GG genotypes can also be associated with decreased MTHFR enzyme activity, although typically less so than the C677T mutation.

23andMe MTHFR Gene Mutations

Mutations in the MTHFR gene are quite common and can affect the function of the MTHFR enzyme. The severity of the impact on the enzyme’s function depends on whether a person carries one or two copies of the mutation.

The C677T mutation is the most common and most well-studied. If a person has one copy of this mutation (heterozygous), the efficiency of the MTHFR enzyme is reduced by about 35%.

If a person has two copies (homozygous), the efficiency is reduced by about 70%.

When the function of the MTHFR enzyme is compromised due to these mutations, it may lead to elevated homocysteine levels, especially if the person’s diet is low in folate.

High homocysteine levels are associated with a higher risk of cardiovascular disease and other conditions.

However, it’s important to note that having an MTHFR mutation does not guarantee that an individual will have high homocysteine levels or any associated health problems.

Many people with MTHFR mutations are healthy and have normal homocysteine levels.

The impact of these mutations can be influenced by other genetic and lifestyle factors, including diet, stress, and overall health.

For people who do have high homocysteine levels or who have a known MTHFR mutation, consuming adequate amounts of folate and possibly supplementing with the active form of folate (5-methyltetrahydrofolate or 5-MTHF) may help to manage homocysteine levels.

References

“MTHFR gene”. Genetics Home Reference. U.S. National Library of Medicine. Retrieved on 2021-02-15.
Refsum H, Nurk E, Smith AD, et al. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr. 2006;136(6 Suppl):1731S-1740S.
Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics. 2001;1
Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998;64(3):169-172.
Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111-113.