['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.', '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.', '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.'] Does methylenetetrahydrofolate reductase polymorphism determine the plasma homocysteine-lowering effect of large-dose folic acid supplementation in patients with cardiovascular disease?