Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations
Jacques, P.F.; Bostom, A.G.; Williams, R.R.; Ellison, R.C.; Eckfeldt, J.H.; Rosenberg, I.H.; Selhub, J.; Rozen, R.
Circulation 93(1): 7-9
1996
ISSN/ISBN: 0009-7322 PMID: 8616944 Document Number: 457969
Background: Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbon donor in remethylation of homocysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated plasma levels of the amino acid homocysteine. Methods and Results: To assess the potential interaction between this mutation and vitamin coenzymes in homocysteine metabolism, we screened 365 individuals from the NHLBI Family Heart Study. Among individuals with lower plasma folate concentrations ( lt 15.4 nmol/L), those with the homozygous mutant genotype had total fasting homocysteine levels that were 24% greater (P lt .05) than individuals with the normal genotype. A difference between genotypes was not seen among individuals with folate levels gtoreq 15.4 nmol/L. Conclusions: Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons.