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

• Published in: American journal of hypertension 2007-07, Vol.20 (7), p.764-770
• Main Authors: Henskens, Léon H., Kroon, Abraham A., van der Schouw, Yvonne T., Schiffers, Paul M., Grobbee, Diederick E., de Leeuw, Peter W., Bots, Michiel L.
• Format: Article
• Language: English
• Subjects: Aged; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endocrine kidney. Renin-angiotensin-aldosterone system; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; genetics; Genotype; Humans; Medical sciences; Middle Aged; Netherlands; nitric oxide synthase; Nitric Oxide Synthase Type III - genetics; Polymorphism, Single Nucleotide; population-based; Receptor, Angiotensin, Type 1 - genetics; Renin-angiotensin system; Risk Factors; stroke; Stroke - genetics; Vertebrates: endocrinology
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2007.02.012

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 A 1166C) and endothelial nitric oxide synthase (NOS3 G 894T) and the risk of stroke. 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. 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 G 894T polymorphism, however, was not associated with stroke risk. In the presence of other coexisting risk factors the AGTR1 A 1166C but not the NOS3 G 894T 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.