By Bethann Hromatka, Ph.D.
The MTHFR gene codes for a protein that helps people metabolize B-vitamin folate (also called folic acid or vitamin B9). Relatively common variations in the DNA sequence – the order of A’s, T’s, G’s and C’s in the gene – can impact how someone metabolizes folate and, in some instances, can impact your health.
More on Folate
People with slight impairments in folate metabolism are usually perfectly healthy since they consume enough folate in their diets to make up for their reduced ability to break it down.
But there are situations – namely during pregnancy – when women with a particular variation in the MTHFR gene called C677T should consume more folate to prevent birth defects. Although all pregnant women are advised to take folic acid supplements because this nutrient is vital for early fetal development, women with the C677T genetic variant appear to need even more of it.
MTHFR and Pregnancy
Scientists have also investigated if the MTHFR gene impacts a woman’s ability to carry a pregnancy to term, but findings aren’t completely convincing. Some studies have found an association between miscarriage and MTHFR variants including C677T in certain populations, but other studies have failed to see a connection. One study added a twist by suggesting that some MTHFR variants predispose for chromosomal abnormalities in the embryo that are incompatible with life and lead to miscarriage. But this study was relatively small and has not been replicated.
Some prospective mothers with a history of miscarriages are being told to test for MTHFR variants with the advice that it ‘can’t hurt.’ But the evidence is that MTHFR gene testing might not actually do any good either.
Regardless of whether the MTHFR variants influence miscarriage, low folate levels and hyperhomocysteinemia in the mother have been linked to recurrent miscarriage. Some women may undergo testing for folate levels or hyperhomocysteinemia if they’ve had multiple miscarriages.
Understanding why miscarriage occurs in the first place is still an active area of research. At least half of miscarriages arise due to major genetic abnormalities in the embryo (for instance missing an entire chromosome). But other factors such as hormonal changes, diet, or whether a woman drinks alcohol or smokes, may also play a role.
Researchers have also studied the MTHFR gene in the context of male infertility. But similar to the case of miscarriage, there isn’t convincing evidence that genetic differences in this gene influence fertility in men.
The Role of MTHFR in Health
The MTHFR gene codes for a protein called methylenetetrahydrofolate reductase that converts one form of folate (5,10-methylenetetrahydrofolate) into a different form of folate (5-methyltetrahydrofolate).
This step in folate metabolism is required for another chemical reaction in the body — specifically for the conversion of an amino acid called homocysteine into another amino acid called methionine that is important for building proteins.
Mutations that cause the MTHFR protein to malfunction may in turn cause someone to accumulate too much homocysteine and develop a condition called hyperhomocysteinemia. Hyperhomocysteinemia has been tentatively linked to a variety of conditions including cardiovascular disease, stroke, and Alzheimer’s disease.
