Methylenetetrahydrofolate reductase mutation (677C -> T) negatively influences plasma homocysteine response to marginal folate intake in elderly women

Individuals who are homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation have depressed serum folate (SF) and elevated p lasma total homocysteine (tHcy) concentrations, which may affect folate req uirements and increase the risk for coronary artery disease. A controlled m etabolic study (14 weeks) using a depletion/repletion protocol was performe d in women (aged 60 to 85 years, N = 33) to provide age-specific data on th e effects of the MTHFR mutation on SF and tHcy status. Subjects consumed a moderately folate-deplete diet (118 mug/d) for 7 weeks, followed by 7 weeks of folate repletion with 200 or 415 mug/d provided as two different treatm ents. Following folate depletion, the mean SF concentration was lower for h omozygous (P = .017) versus heterozygous subjects. Homozygotes for the 677C --> T mutation showed a higher (P = .015) percent increase in plasma tHcy (44%) than heterozygous (20%) or normal (15%) subjects. At week 7, the mean plasma tHcy concentration was higher in homozygous subjects (12.5 +/- 5.3 pmol/L, mean +/- SD) versus the heterozygous (10.8 +/- 3.8 mu mol/L, P = .0 08) or normal (11.3 +/- 2.7 mu mol/L, P = .001) genotype groups. Following folate repletion, plasma tHcy concentrations were not different between gen otype groups, despite a higher (P < .016) SF concentration in subjects with the homozygous genotype. These data suggest that older women who are homoz ygous for the MTHFR 677C --> T mutation may be at risk for greater elevatio ns in plasma tHcy in response to moderately low folate intake as compared w ith individuals with the normal or heterozygous genotypes. Copyright (C) 20 00 by W.B. Saunders Company.