METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM - RELATION TO BLOOD-PRESSURE AND CEREBROVASCULAR-DISEASE

Hyperhomocysteinemia is reported to be associated with an increase in the incidence of ischemic heart disease and cerebrovascular disease. G enetic aberrations in methylenetetrahydrofolate reductase (MTHFR) may account for reduced enzyme activity and elevated plasma homocysteine l evel. A recent report revealed that a common mutation (677C to T; Ala to Val) in the MTHFR gene is associated with decreased specific MTHFR activity and with increased risk for coronary artery disease in the ho mozygous state (Val/Val). In the present study, we investigated whethe r the MTHFR gene is a genetic risk factor for cerebrovascular disease (CVD). To undertake a case-control study, we selected the patients wit h cerebral infarction (n = 48) or cerebral hemorrhage (n = 35) and exa mined the association between MTHFR gene polymorphism and CVD. The gen otype distribution of the MTHFR gene was not significantly different b etween cases and controls. Because the possibility of matching the mor bidity of the effects of hypertension, the lack of association could n ot be excluded in the first study; however, we also examined whether t he MTHFR mutation was associated with any clinical risk factor for CVD or with hypertension. It turned out that the subjects with the Val al lele of the MTHFR gene had significantly lower blood pressure than the subjects with other genotypes in the general population (P = .02), an d that the frequency of the Val/Val genotype in hypertensive subjects (n = 173) was significantly lower than in control subjects (n = 184) ( P = .03). From these results, we conclude that the Val/Val homozygous state of the MTHFR gene increased the risk of thrombosis, but reduced the blood pressure, which resulted in the lack of increased risk for C VD. Am J Hypertens 1998;11:1019-1023 (C) 1998 American Journal of Hype rtension, Ltd.