Variants Around miR-451 Can Affect the Risk of Large-artery Atherosclerosis Stroke in Chinese

Abstract Background: Ischemic stroke has high incidence rate, mortality rate and disability rate. Genetic factors have a significant impact on stroke risk. MicroRNAs are a class of small non-coding RNA. Intergenic variants can affect the regulation of microRNAs and modulate large-artery atherosclerosis stroke susceptibility. The low expression of miR-451 aggravated ischemic injury significantly.Methods: Functional intergenic variants near hsa-mir-451 were identified by bioinformatics analysis. We conducted a case-control study to explore the associations of selected variants with large-artery atherosclerosis stroke risk in Chinese.Results: The rs901975 (G>A) near hsa-mir-451 was identified as a functional SNP for stroke susceptibility. The protective effect of A allele was significant in codominant model (OR = 0.62, 95% CI = 0.44-0.89, P = 0.005), recessive model (OR = 0.65, 95% CI = 0.47-0.89, P = 0.006) and log-additive model (OR = 0.82, 95% CI = 0.71-0.96, P = 0.012). We also found the significant effect in participants over 65 years old, male, hypertensive and diabetic people. Moreover, hypertensive people genotyped as GG+GA had 2.84 - fold increased risk compared with those genotyped as AA without hypertension (P interaction = 0.036). In the MEGASTROKE Consortium, rs901975 A allele also had protective effect on LAA stroke in Europeans (OR = 0.937, 95% CI: 0.882-0.996, P = 0.036). Combined analysis of our study and MEGASTROKE showed consistent trend (OR = 0.920, 95% CI: 0.869-0.973, P = 0.004).Conclusions: Our study suggested that rs901975 near hsa-mir-451 might affect large-artery atherosclerosis stroke susceptibility in Chinese population.