A Common Polymorphism in the Methylenetetrahydrofolate Reductase Gene, Homocysteine, and Ischemic Cerebrovascular Disease

BACKGROUND AND PURPOSE: A common polymorphism (T/t) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) enzyme has been associated with elevated serum homocysteine, itself a risk factor for stroke. Some studies have reported an association with ischemic heart disease, but no published studies have examined its relationship with stroke. METHODS: We determined the TT genotype frequency and T allele frequency in 345 patients with ischemic cerebrovascular disease (CVD) and 161 control subjects. In a subgroup we also determined serum homocysteine and folate concentrations. RESULTS: In the patient group there was a significant relationship between TT genotype and homocysteine concentration after we controlled for other risk factors. Controlling for serum folate weakened this relationship, and folate itself was independently related to serum homocysteine. There was no difference between patients and control subjects in either TT genotype frequency (10.7% versus 13.7%; P = .34) or T allele frequency (0.68 versus 0.67; P = .67). There was no association when analysis was limited to individuals deficient in folate (serum folate < 25th centile) or to younger individuals (< 65 years). There was no association between TT genotype and any stroke subtype or with degree of carotid stenosis. CONCLUSIONS: In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.