Vitamin B9 (folate)

MTHFR · rs1801133 + rs1801131

Folate (vitamin B9) supplies methyl groups for DNA synthesis and the remethylation of homocysteine to methionine. The key enzyme MTHFR carries two common variants that lower its activity and, with scarce folate intake, can mildly raise homocysteine.

The markers

MTHFR reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the main circulating form of folate. C677T (rs1801133, Ala222Val) produces a thermolabile, less active enzyme; the allele is common (around 38 percent of chromosomes) and was described as a risk factor for raised homocysteine and vascular disease (Frosst 1995), confirmed in GWAS for homocysteine (Hazra 2009). A1298C (rs1801131) acts more weakly; the combination of 677T plus 1298C adds up the loss of activity.

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; supplementation is often done directly with L-5-methylfolate. The once-popular idea that MTHFR variants explain numerous complaints does not hold up. The dedicated MTHFR page goes deeper into the enzyme and guidelines.

Context

Professional bodies advise against routine MTHFR testing for thrombosis or pregnancy because the predictive value is low. Genome shows the genotype as metabolic context, not as proof of disease.

What Genome measures. The genotypes at the MTHFR variants rs1801133 (C677T) and rs1801131 (A1298C).

Related topics

MTHFRVitamin B12 (FUT2, CUBN, TCN2)rsIDs, microarray and SNP lookup

Sources

  1. 1Frosst et al., 1995 A candidate genetic risk factor for vascular disease: a common mutation in MTHFR. Nature Genetics 10:111–113. doi.org/10.1038/ng0595-111
  2. 2Hazra et al., 2009 Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. Human Molecular Genetics 18:4677–4687. doi.org/10.1093/hmg/ddp428