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

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.