Evaluation of miR-34b/c polymorphisms to the risk of ischemic stroke

Abstract

Objectives:Polymorphisms in microRNA genes are related to the risk of ischemic stroke, but the association between miR-34b/c polymorphisms and the risk of ischemic stroke has not been reported.Methods:MiR-34b/c rs2187473 and rs4938723 polymorphisms were genotyped by Snapshot assay among 495 controls and 492 ischemic stroke patients. Expression levels of miR-34b and miR-34c were quantified by real-time PCR. Transcriptional activity of miR-34b/c promoter was measured by luciferase reporter assay.Results:Rs4938723 was associated with an increased risk of ischemic stroke in our study (CC versus TT: OR=2.34, 95% CI=1.47-3.72, P=0.001;C versus T: OR=1.37, 95% CI=1.12-1.68, P=0.002; CC versus TT+TC: OR=2.12, 95% CI=1.37-3.29, P=0.001). The expression levels of miR-34b and miR-34c were significantly downregulated in cases by contrast with controls (P<0.05). Further analysis demonstrated that the expression levels of miR-34b and miR-34c were also downregulated in the individuals carrying rs4938723 CC genotype by contrast with that carrying TT+TC genotypes (P<0.05). The result of luciferase reporter assay showed that rs4938723C allele decreased the transcriptional activity of miR-34b/c promoter compared with rs4938723 T allele.Conclusion:Our study showed a positive relation between the miR-34b/c rs4938723 polymorphism and the risk of ischemic stroke, which indicated that rs4938723 may be used for ischemic stroke prediction or therapy in the future.