Genetic polymorphisms in the renin-angiotensin system confer increased risk of stroke independently of blood pressure: a nested case-control study

Objective The renin-angiotensin system has a pathophysiological role in cardiovascular disease through a variety of processes. Polymorphisms in involved genes have been described and implicated in stroke. The aim of this study was to investigate two polymorphisms in two genes in the renin-angiotensin system and the risk of stroke. Design A nested case-control study using baseline data obtained from population-based surveys in northern Sweden was performed. There were 275 individuals without major concomitant disease who suffered a first ever stroke during follow-up and 549 controls matched for age, sex and domicile. Methods Blood samples obtained at baseline were analyzed for potential risk factors including the A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene and the functional insertion/deletion polymorphism of the angiotensin-converting enzyme gene. Results Individuals with the AA genotype of the AT1R gene were at increased risk of ischemic stroke (odds ratio=1.60; P=0.005) compared with those with the AC and CC genotypes. The D allele of the angiotensin-converting enzyme insertion/deletion polymorphism was associated with a higher risk of stroke (odds ratio=1.58; P=0.014). Conclusion In this prospective study, there was an association between A1166C polymorphism in the angiotensin II receptor gene and ischemic stroke. We also replicated previous observations that the D allele of the angiotensin-converting enzyme insertion/deletion polymorphism was associated with increased risk of stroke. The observed elevated stroke risks conferred by these two polymorphisms are independent of each other and common risk factors such as blood pressure, diabetes, smoking and high cholesterol levels.