A Meta-Analysis of the Association between Polymorphisms in MicroRNAs and Risk of Ischemic Stroke.

Yan Xiao,Ju Xiang,Huai-Qing Luo,Jian-Ming Li,Mei-Hua Bao

doi:10.3390/genes6041283

Abstract

Ischemic stroke (IS) is responsible for a high death rate and for adult disability worldwide. MiR-146a (rs2910164), miR-149 (rs2292832), miR-196a2 (rs11614913) and miR-499 (rs3746444) are found to be associated with ischemic stroke. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the four polymorphisms and IS risk. The databases Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched for related studies. A total of five studies including 2230 cases and 2229 controls were identified for the meta-analysis. The results indicate that TT genotype and T allele of miR-149 (rs2292832) are associated with significantly lower risks of IS in a homozygous model (OR = 0.70) and an allelic model (OR = 0.86). No significant associations were found between miR-146a (rs2910164), miR-196a2 (rs11614913), miR-499 (3746444) and IS susceptibility in any of the studies. However, subgroup analysis by sample size indicates a significant decrease in risks of IS for CC genotype and C allele of miR-146a (rs2910164) in the large sample size group. Therefore, miR-149 (rs2292832) might be recommended as a predictor for IS risk, while miR-146a (rs2910164), miR-196a2 (rs11614913), miR-499 (3746444) are not.

Highlights

Being the most common kind of stroke, ischemic stroke (IS) is responsible for a high death rate and adult disability worldwide
MicroRNAs are non-coding, small RNAs with lengths of about 22 nt, which regulate the expression of many genes at a post-transcriptional level by binding to the 3-UTR of target genes [5,6]
In the present study, we included a total of 5 studies, which have 2230 cases and 2229 controls, to get a more precise and comprehensive estimation of the association between the four polymorphisms and IS

Summary

Introduction

Being the most common kind of stroke, ischemic stroke (IS) is responsible for a high death rate and adult disability worldwide. The risk factors of IS include age, smoking, diabetes mellitus, and hyperlipemia. A slight change in the sequence of miRNAs, such as single nucleotide polymorphisms (SNPs), may change their production or affinity to target genes and result in diseases. Polymorphisms in pre-miRNA sequences of miR-146a C>G (rs2910164), miR-149 T>C (rs2292832), miR-196a2 T>C (rs11614913) and miR-499 A>G (rs3746444) have been found [7,8]. The miR-146aG, miR-149T, miR-196a2C, and miR-499G alleles are possible genetic predisposing factors, and may associate with ischemic stroke. In the present study, we included a total of 5 studies, which have 2230 cases and 2229 controls, to get a more precise and comprehensive estimation of the association between the four polymorphisms and IS

Methods

Results

Discussion

Conclusion