Methylenetetrahydrofolate reductase is a riboflavin-dependent (FAD) enzyme that catalyzes the NADPH-dependent reduction of 5,10-methylene-tetrahydrofolate (THF) to 5-methyl-THF, and is a key enzyme in the folate metabolism pathway – directing folate from the diet either to DNA synthesis or homocysteine remethylation, a process by which homocysteine is converted back to Methionine. The two polymorphisms described occur at relatively high frequencies in the population, approximately 10-30%, and lower the activity of the MTHFR enzyme.
MTHFR 677C>T polymorphism
The T allele reduces the stability and lowers activity of the MTHFR enzyme, which results in an increase in homocysteine levels, a decrease in DNA methylation, and thus an increase in DNA adducts. T allele carriers have increased folate, vitamin B2, B6 and B12 requirements. Enzyme function is only 70% of optimal in CT individuals and 30-40% of optimal in TT in individuals.
MTHFR 1298 A>C polymorphism
The C allele affects enzyme regulation by S-adenosylmethionine (SAMe), and is associated with decreased enzyme function.
Hustad, S. et al., 2007., Miyaki, K., 2010. & Stover, PJ., 2011.