There is increasing evidence suggesting that dysregulation of miR-155 and its target angiotensin receptor type 1 (AT1R) are linked to the incidence of ischemic stroke (IS), but the underlying mechanisms remain to be clarified. In this study, we therefore sought to investigate how miR-155 and AT1R polymorphisms affect IS risk. We included 579 IS patients and 509 age-matched controls in the present analysis, genotyping individuals for the rs767649 polymorphism in miR-155, as well as for the rs1492099 and rs275653 polymorphisms in AT1R via iMLDR-TM genotyping technology. The allele and genotype frequencies for the assessed polymorphisms were comparable in IS patients and controls, without any detectable association between AT1R haplotype and IS risk. We conducted additional trial of ORG 10172 in acute stroke treatment-mediated stratification, which indicated that the AT1R rs1492099 T allele was linked to a decreased risk of large-artery atherosclerosis (LAA) stroke. We further found that those with the AT1R rs275653 AA genotype had a decreased risk of small-artery occlusion (SAO) strokes. We further confirmed elevated miR-155 expression in IS patients, but observed no link between the rs767649 polymorphism and expression of this microRNA. Similarly, rs1492099 and rs275653 polymorphisms did not impact AT1R expression levels. The miR-155 rs767649 polymorphism does not seem to be a key determinant of IS risk, whereas the AT1R rs1492099 polymorphism is linked to reduced LAA-stroke risk, and the rs275653 AA genotype is potentially protective against SAO strokes.
Keywords: angiotensin receptor type 1; case-control; ischemic stroke; miR-155; polymorphism.