What is Methylenetetrahydrofolate Reductase C677T Polymorphism?
The MTHFR gene encodes methylenetetrahydrofolate reductase, the enzyme that converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine to methionine. The C677T polymorphism (rs1801133) results in an alanine-to-valine substitution that renders the enzyme thermolabile and reduces its activity to approximately 65% in heterozygotes and 30% in homozygotes. Reduced MTHFR activity impairs folate metabolism and can lead to elevated plasma homocysteine, particularly when folate status is suboptimal.