WATCH: How to interpret your MTHFR report
What is MTHFR?
The methylenetetrahydrofolate reductase (MTHFR) gene carries instructions for the production of an enzyme with the same name.
This important enzyme is associated with the processing of amino acids, which are the building blocks for protein molecules.
In the MTHFR pathway, the enzyme converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate.
This is one of the steps in the process that converts the ‘ harmful’ amino acid homocysteine to the ‘useful’ amino acid, methionine.
MTHFR gene mutations
All of us have the MTHFR gene. But the type of MTHFR gene differs from person to person.
To explain this better, let’s take the example of blood groups. All of us have red blood. But you may have O+ve blood type, while the other person may be A-ve - and these different blood groups have different health implications.
Like how O+ve and A+ve are the most common blood types, the MTHFR gene also has 2 common variants (type): C677T and A1298C, the former being more common than the latter.
About 40% of the American population have the C677T type, which has been associated with up to 80% reduction in the enzyme’s efficiency
This reduction has been found to lead to increased levels of homocysteine, which in turn increases the risk of venous thrombosis and heart disease.
Once you learn about the type of MTHFR gene you carry, its effects can be ameliorated by simple fixes such as dietary changes and folic acid supplements.
How common are the MTHFR mutations?
MTHFR mutation prevalence in the U.S,
MTHFR C677T mutation is the most common and is found at a higher frequency in certain ethnic populations.
- 20% to 40% of white and Hispanic people are found to be heterozygous to this MTHFR gene
- 1%–2% among blacks
MTHFR C677T: Homozygous vs. Heterozygous
MTHFR mutations are typically referred to as heterozygous or homozygous. Heterozygous means only one copy of the variant allele, which here is T. So the person's MTHFR gene type will be CT.
Homozygous means two copies of the variant allele - TT
MTHFR mutation prevalence in North America, Australia, and Europe
- 8% to 20% are homozygous for MTHFR C677T
- 7% to 12% have the 23andme MTHFR A1298C mutation
What Does A Positive MTHFR Mean?
A positive MTHFR test result indicates that you have any of the above-mention change in one or both copies of your MTHFR gene.
While only one copy of the change is less likely to cause any health issues, two copies can significantly increase your risk for conditions associated with higher homocysteine levels.
How to find MTHFR on 23andMe?
23andMe provides your genomic information in the form of raw data that can be easily accessed and then uploaded onto sites like Xcode Life to find out the specific variant carried.
23andMe MTHFR results for rs1801133 (MTHFR C677T)
| AA | 2 copies of the variant allele, reduction in MTHFR enzyme activity by nearly 80% |
| AG | 1 copy of the variant allele, reduction in MTHFR enzyme activity by 40% |
| GG | Both normal alleles, no reduction in enzyme activity due to this polymorphism |
23andMe MTHFR results for rs1801131 (A1298C)
| GG | 2 copies of the variant allele, reduction in MTHFR enzyme activity |
| GT | 1 copy of the variant allele, reduction in MTHFR enzyme activity |
| TT | Both normal alleles, no reduction in enzyme activity due to this polymorphism |
Apart from 23andMe, raw data from companies like AncestryDNA.com, FTDNA.com, and other similar genetic testing service providers may be uploaded to find out more about your MTHFR gene mutations.
What is the difference between 23andMe MTHFR test and AncestryDNA MTHFR test?
| Contents | MTHFR status from 23andme raw data | MTHFR status from Ancestry DNA raw data |
|---|---|---|
| Raw data | 23andme raw data can be downloaded | Ancestry DNA raw data can be downloaded |
| MTHFR C677T and A1298C | 23andme MTHFR test includes these two SNPs | AncestryDNA MTHFR test includes these two SNPs |
| MTHFR test cost | 23andme test cost is $99 | Ancestry DNA test cost is $99 (with a 10% discount on offer currently) |
| MTHFR test report | 23andme report does not include information on MTHFR gene. Information is present as raw data which needs interpretation. | Ancestry report does not include information on MTHFR gene. Information is present as raw data which needs interpretation. |
| MTHFR gene report from Alternate providers | A variance report generated using 23andme raw data V5 chip has less number of SNPs compared to ancestry DNA. | A variance report generated using Ancestry DNA raw data has more number of SNPs compared to 23andme V5 chip. |
Health implications of MTHFR mutations
Here are a few studies which show an association with various health conditions among people with the different types of the MTHFR gene.
- Association of MTHFR gene polymorphism with cardiovascular disease (CVD)
In a large meta-analysis conducted on over 40 studies that included 11162 cases and 12758 controls, individuals with the TT type (C677T) were associated with a higher risk for CVD. - Association of MTHFR gene polymorphism with Breast Cancer risk
There are two ways in which the MTHFR gene types can influence cancer risk.
In the MTHFR pathway (a series of biochemical events in the body involving the MTHFR gene), the substrate (the part that reacts with the enzyme) 5,10- methylenetetrahydrofolate, of the MTHFR enzyme, is associated with the production of another chemical, deoxythymidylate monophosphate (DMP), from deoxyuridylate monophosphate(DOMP).
When the amount of substrate is reduced, it could affect the ratio of DMP/DOMP.
This, in turn, would increase the addition of uracil, instead of thymine, resulting in an increased risk for point mutation and breakage of DNA.
An alternate mechanism for an increase in breast cancer risk is by the level of methionine, as this amino acid is necessary for maintaining healthy methylation patterns in DNA.
A meta-analysis showed that people with the TT genetic type were associated with an increased risk for breast cancer.
- Association of MTHFR gene polymorphism with Venous thromboembolism
Deep vein thrombosis or pulmonary embolism (happens when a blood clot travels to your lung and blocks the blood flow) is one of the major risk factors of morbidity and mortality among older adults.
Among 70 individual studies, it was found that people with the TT genetic type had higher homocysteine levels, thereby increasing their risk for deep vein thrombosis. - Association of MTHFR gene polymorphism with Autism spectrum Disorders
Certain types of MTHFR gene have been found to alter the MTHFR enzyme activity, which has been shown to affect neurological development.
Children with the TT genetic type were associated with an increased risk of autism spectrum disease in countries where the food was not fortified with folate. - Association of MTHFR gene polymorphism with neural tube defects
In a meta-analysis, 40 studies were taken into consideration and it was found that mothers with the C677T genetic type were associated with an increased risk for neural tube defects (birth defects in the brain and spine)
According to the NIH, there are over 40 mutations in the MTHFR gene that are associated with poor enzyme activity and the associated increase in homocysteine levels in the body.
Certain genetic testing companies check for only the two major MTHFR gene mutations, while there are many others, like us, who give you a detailed report based on the 23andme MTHFR variants present in the 23andme raw data.
The Xcode Life MTHFR report covers several of these genetic variations covered in the NIH publication above.
More About MTHFR Gene Mutations
Is C677T with a TT genotype the same as C677T with an AA genotype?
Hi Katy, thanks for getting in touch with us. In the 677th position in the MTHFR gene, people either have the C allele (more common) or the T allele - so the possible genotypes are CC, CT, and TT. A is complementary to T on the opposite strand of the DNA. Hope this clarifies!
Hello,
I’m confused with my results. I’ve got
RS1801133 GG ( normal enzyme activity)
RS1801131 GG. ( reduced enzyme activity)
Moderately likely moderate lower MTHFR Enzyme activity.
Does this make me Heterozygous or Homozygous?
Thanks in advance.
Hello Ben! In rs1801133, you are homozygous for the major allele (C or G), which implies a likelihood of normal MTHFR enzyme activity. In rs1801131, you are homozygous for the variant allele (C or G). which implies a likelihood of reduced MTHFR enzyme activity. Overall, this translates to a likelihood of moderately reduced enzyme activity.
Severely decreased activity 677TT, 1298AA. Has anyone sought treatment or supplementation for MTHFR? How did it go? Having trouble finding a doctor that has knowledge and have been self treating with methylfolate.
Thanks so touch for this article. I had recent blood work done and noticed a reduced RBC folate and elevated homocysteine. Armed with this information I found your article and looked into the raw data from my 23andMe test I'd had done this spring. Lo and behold, I see I have the MTHFR A1298C mutation GT (one copy of the variant allele). Now, I can consider supplementation to counter this.
Confusing. C677T (rs1801133) is A or G on 23and me - not T or C. What is a TT genotype for this then?
A TT genotype implies 2 copies of variant allele, and nearly an 80% reduction of the MTHFR enzyme activity.
Great article! MTHFR sure is one tricky gene. Can you tell me if I can use my Living DNA raw data to get this report? Thanks!
Thank you. I am glad you liked the article. Yes, you can upload your living DNA raw data to get the MTHFR report.