Renin-Angiotensin System and Nitric Oxide Synthase Gene Polymorphisms in Relation to Stroke

Background There is ample evidence that genetic factors contribute to cardiovascular disease risk. The present study aimed to assess the relation between polymorphisms of the angiotensin II type 1 receptor (AGTR1 A1166C) and endothelial nitric oxide synthase (NOS3 G894T) and the risk of stroke. Methods We performed a case-cohort study on all first fatal and nonfatal stroke events (n = 74) and a 10% random sample (n = 1523) of a population-based cohort of women aged 49 to 70 years (n = 15,236; median follow-up 4.3 years). Univariate and multivariate unweigthed Cox proportional hazards regression models were used to assess the relation between the polymorphisms, their interactions with coexisting risk factors, and the risk of stroke. Results The relation between the AGTR1 CC genotype and stroke risk (unadjusted hazards ratio [HR] 1.62; 95% confidence interval [CI], 0.81–3.28) was modified by increasing age (>56 years: adjusted HR 2.77; 95% CI, 1.17–6.56) and systolic blood pressure (BP) (>130 mm Hg: adjusted HR 2.58; 95% CI, 1.12–5.93). The NOS3 G894T polymorphism, however, was not associated with stroke risk. Conclusions In the presence of other coexisting risk factors the AGTR1 A1166C but not the NOS3 G894T polymorphism increased the risk of stroke. The CC genotype may help identify those individuals who are at greatest risk and who may need (early) treatment or careful follow-up.