MTHFR

rs1801133 + rs1801131

MTHFR encodes a key enzyme of folate and methylation metabolism. Two common variants reduce enzyme activity and can mildly raise homocysteine. Its clinical importance was long overstated; with good folate supply the effect is usually small.

The two variants

C677T (rs1801133, amino acid change alanine to valine) produces a thermolabile enzyme with reduced activity. A1298C (rs1801131) lowers activity more weakly. Both are common in the population. What matters most is the combination of reduced activity and scarce folate supply.

What it means

A slowed folate cycle can mildly raise homocysteine. The effect is usually small and can be offset by sufficient folate and B vitamins. The once-popular idea that MTHFR variants explain numerous complaints does not hold up to the evidence.

Context

The American College of Medical Genetics advises against routine MTHFR testing because its predictive value for thrombosis and pregnancy complications is low. Genome shows the genotype as technical evidence, not as proof of disease.

What Genome measures. The genotypes at rs1801133 (C677T) and rs1801131 (A1298C) and the resulting tendency of enzyme activity.

Related topics

rsIDs, microarray and SNP lookupVDR (vitamin D receptor)Disease associations

Sources

  1. 1Frosst et al., 1995 A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics 10:111–113. doi.org/10.1038/ng0595-111
  2. 2Hickey et al., 2013 ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genetics in Medicine 15:153–156. doi.org/10.1038/gim.2012.165