Methylenetetrahydrofolate reductase polymorphism determines the plasma homocysteine-lowering effect of large-dose folic acid supplementation in patients with cardiovascular disease

Objective The polymorphism of the gene encoding methylenetetrahydrofolate reductase (MTHFR) and folic acid nutritional status play important roles in atherosclerosis. The present study investigated the total homocysteine-lowering effect of folic acid in response to the MTHFR genotype in patients who have cardiovascular disease. Methods Twenty-three patients who had cardiovascular disease (ages 44 to 88 y) were supplemented with 5 mg of folic acid/d for 8 wk. Blood samples were collected before and after supplementation for the measurement of folic acid. The presence of the 677C→T mutation was assessed by polymerase chain reaction followed by restriction enzyme analysis. Results After the 8 wk of folic acid supplementation, plasma total homocysteine decreased 40% in patients who had the TT genotype, 23% in those who had the CT genotype, 10% in those who had the CC genotype, and 27% in carriers of the T allele. The plasma total homocysteine-lowering effect of folic acid was significant only in patients who had the CT genotype and in carriers of the T allele. Conclusions The MTHFR polymorphism may be involved in the total homocysteine-lowering effect of folic acid in patients who have cardiovascular disease.