RELATION BETWEEN FOLATE STATUS, A COMMON MUTATION IN METHYLENETETRAHYDROFOLATE REDUCTASE, AND PLASMA HOMOCYSTEINE CONCENTRATIONS

Background Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-m ethyltetrahydrofolate, the major carbon donor in remethylation of homo cysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated p lasma levels of the amino acid homocysteine. Methods and Results To as sess the potential interaction between this mutation and vitamin coenz ymes in homocysteine metabolism, we screened 365 individuals from the NHLBI Family Heart Study. Among individuals with lower plasma folate c oncentrations (<15.4 nmol/L), those with the homozygous mutant genotyp e had total fasting homocysteine levels that were 24% greater (P<.05) than individuals with the normal genotype. A difference between genoty pes was not seen among individuals with folate levels greater than or equal to 15.4 nmol/L. Conclusions Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocyst eine concentrations; folate supplementation may be necessary to preven t fasting hyperhomocysteinemia in such persons.