A COMMON POLYMORPHISM IN THE METHYLENETETRAHYDROFOLATE REDUCTASE GENE, HOMOCYSTEINE, AND ISCHEMIC CEREBROVASCULAR-DISEASE

Background and Purpose A common polymorphism (Tit) in the gene encodin g the methylenetetrahydrofolate reductase (MTHFR) enzyme has been asso ciated with elevated serum homocysteine, itself a risk factor for stro ke. Some studies have reported an association with ischemic heart dise ase, but no published studies have examined its relationship with stro ke. Methods We determined the TT genotype frequency and T allele frequ ency in 345 patients with ischemic cerebrovascular disease (CVD) and 1 61 control subjects. In a subgroup we also determined serum homocystei ne and folate concentrations. Results In the patient group there was a significant relationship between TT genotype and homocysteine concent ration after we controlled for other risk factors. Controlling for ser um folate weakened this relationship, and folate itself was independen tly related to serum homocysteine. There was no difference between pat ients and control subjects in either TT genotype frequency (10.7% vers us 13.7%; P=.34) or T allele frequency (0.68 versus 0.67; P=.67). Ther e was no association when analysis was limited to individuals deficien t in folate (serum folate <25th centile) or to younger individuals (<6 5 years). There was no association between TT genotype and any stroke subtype or with degree of carotid stenosis. Conclusions In patients wi th CVD we confirmed a relationship between the MTHFR genotype and seru m homocysteine concentration and an interaction with serum folate conc entration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could sti ll be a risk factor in populations with a low folic acid intake.