MTHFR

About MTHFR

MTHFR on chromosome 1p36.22 encodes methylenetetrahydrofolate reductase, which converts 5,10 methylenetetrahydrofolate to 5 methyltetrahydrofolate, the main circulating form of folate, which provides the methyl group used to remethylate homocysteine to methionine. Two common variants, C677T and A1298C, have been widely studied. People homozygous for C677T have a thermolabile enzyme with reduced activity and may have mildly elevated homocysteine, particularly when folate intake is low. These homozygotes are common, with frequencies varying widely between populations. Despite extensive direct to consumer testing and supplement marketing, common MTHFR variants have shown little clinical significance in large studies, and professional bodies including the American College of Medical Genetics and Genomics have advised against routine MTHFR testing, for example in the evaluation of blood clots or recurrent pregnancy loss. Folic acid fortification of grain products, mandatory in the United States since 1998, has reduced neural tube defects at the population level. Elevated homocysteine from any cause is associated with cardiovascular disease, but trials that lowered homocysteine with B vitamins did not reduce cardiovascular events. Rare severe MTHFR deficiency, caused by variants on both copies, is a distinct autosomal recessive disorder with homocystinuria and neurological problems.