Gene polymorphisms of the renin-angiotensin-aldosterone system and the risk of ischemic stroke: a role of the A1166C/AT1 gene variant

Objective The role of the renin-angiotensin-aldosterone system (RAAS) genes on predisposition to develop stroke, a multifactorial and polygenic cardiovascular trait, is still under investigation. In the present study we characterized the contributory role of RAAS genes in the susceptibility to develop ischemic stroke in humans. Methods Allele and genotype frequencies of RAAS genes were characterized in a population of 215 cases (including only atherothrombotic and lacunar forms) and 236 controls selected in Sardinia, a large Mediterranean island with a well-known segregated population. Statistical analysis was performed in the whole population and, based on a significant interaction between angiotensin II receptor (AT1) genotype and hypertension, was also repeated in the hypertensive subgroup. Results A significant association of the C1166/AT1 gene allelic variant with stroke was found when assuming a dominant model of transmission [unadjusted odds ratio (OR) = 1.5, 95% confidence interval (Cl) 1.1-2.2, P = 0.024]. The strength of the association became more evident in the subgroup of hypertensive individuals (135 cases and 110 controls). In fact, in this cohort the independent OR for the AT1 gene was 2.1, 95% Cl 1.2-3.7, P = 0.006 in the dominant model and 2.0, 95% Cl 1.3-3.2, P= 0.002 in the additive model. No other RAAS gene was identified as a contributor to stroke. Conclusions Our findings support a predisposing role of an AT1 gene variant in the development of ischemic stroke. In particular, the AT1 gene variant exerted a major impact on ischemic stroke occurrence in the presence of hypertension.