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 A(1166)C) and endothelial nitric oxide synthase (NOS3 G(894)T) 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 G(894)T polymorphism, however, was not associated with stroke risk.


CONCLUSIONS
In the presence of other coexisting risk factors the AGTR1 A(1166)C but not the NOS3 G(894)T 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.
Henskens
Léon H
LH
Department of Internal Medicine, Division of General Internal Medicine, Subdivision Vascular Medicine, University Hospital Maastricht and Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Kroon
Abraham A
AA
van der Schouw
Yvonne T
YT
Schiffers
Paul M
PM
Grobbee
Diederick E
DE
de Leeuw
Peter W
PW
Bots
Michiel L
ML
D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009426:Netherlands; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*
D044140:Receptor, Angiotensin, Type 1; D052250:Nitric Oxide Synthase Type III