Genetic variants of miR-146a and miR-499 and risk of ischemic stroke in the Chinese population: a meta-analysis and trial sequential analysis

Objective: Genetic variants in miRNA sequences may alter miRNA expression and/or maturation, resulting in diverse functional consequences. The aim of the present meta-analysis was to investigate the association between miR-146a rs2910164 and miR-499 rs3746444 genetic polymorphisms and risk of ischemic strokes (IS) in the Chinese population. Methods: A literature search was conducted using PubMed, EMbase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases up to October 2017. Pooled effects (odds ratio [OR] together with 95% confidence intervals [CI]) were calculated. Subgroup analyses were carried out by status of Hardy-Weinberg equilibrium, sample size, genotyping methods, and subtypes of IS. Trial sequential analysis (TSA) was used to reduce the risk of type I errors and determine whether the evidence was firm. Results: A total of 10 eligible studies, consisting of 4,251 patients with IS and 5,812 controls, were finally included. Results showed that pooled OR for IS of the rs2910164 G allele was 1.23 (95% CI: 1.03-1.46, P = 0.022), compared to wild-type C allele under a recessive model, with high heterogeneity (I2 = 56.2%, P = 0.015). No significant association was found between the rs3746444 variant and IS under different genetic models. TSA showed a solid conclusion for association between the rs2910164 variant and IS risk. Conclusion: Current evidence suggests a weak association between miR-146a rs2910164 variant and risk of IS, whereas miR-499 rs3746444 variant might not be associated with elevated risk of IS in a Chinese population.