Genetic Variants Associated with High Susceptibility of Premature Ischemic Stroke

Abstract

Background. Several polymorphisms had been associated with an increased risk of ischemic stroke, but results are inconclusive. The aim of this study was to examine the association between AGTR1 A1166C and TSP-1 N700S polymorphisms and ischemic stroke in a young Mexican population. Methods. In a case-control study, 250 $\text{patients}\le 45$ years of age with ischemic stroke and 250 controls matched by age and gender were included. The polymorphisms were determined in all participants by polymerase chain reaction. Results. There were statistical differences in genotype distribution ( $p=0.01$ ) and allele frequency ( $p=0.001$ ) of AGTR1 A1166C polymorphism. In contrast, there was a similar genotype distribution ( $p=0.96$ ) and allele frequency ( $p=0.76$ ) of the TSP1 N700S genetic variant between groups. Hypertension ( $p=0.03$ ), smoking ( $p=0.02$ ), and family history of atherothrombotic disease ( $p=0.04$ ) were associated with stroke, but not diabetes ( $p=0.30$ ) and dyslipidemia ( $p=0.08$ ). Conclusions. This is the first study in Mexican population to explore several genetic variants in young patients with ischemic stroke. Our results suggest that polymorphisms in the renin-angiotensin-aldosterone system could contribute to premature hypertension, endothelial dysfunction, atherothrombosis, vasoconstriction, smooth muscle cell migration, and proliferation. In contrast, polymorphisms in the coagulation factors are not associated with ischemic stroke. Environmental factors such as diabetes and dyslipidemia could be less important in the pathogenesis of ischemic stroke at a young age. We suggest that those polymorphisms should be determined in individuals with a family history of thrombosis to avoid the stroke development. Therefore, genotype-environmental combination could determine several possible phenotypes at different moments in life.