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 plasma total homocysteine (tHcy) concentrations, which may affect folate requirements and increase the risk for coronary artery disease. A controlled metabolic study (14 weeks) using a depletion/repletion protocol was performed in women (aged 60 to 85 years, N = 33) to provide age-specific data on the effects of the MTHFR mutation on SF and tHcy status. Subjects consumed a moderately folate-deplete diet (118 μg/d) for 7 weeks, followed by 7 weeks of folate repletion with 200 or 415 μg/d provided as two different treatments. Following folate depletion, the mean SF concentration was lower for homozygous (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 μmol/L, mean ± SD) versus the heterozygous (10.8 ± 3.8 μmol/L, P = .008) or normal (11.3 ± 2.7 μmol/L, P = .001) genotype groups. Following folate repletion, plasma tHcy concentrations were not different between genotype groups, despite a higher (P < .016) SF concentration in subjects with the homozygous genotype. These data suggest that older women who are homozygous for the MTHFR 677C → T mutation may be at risk for greater elevations in plasma tHcy in response to moderately low folate intake as compared with individuals with the normal or heterozygous genotypes. Copyright © 2000 by W.B. Saunders Company