Association of the genetic polymorphisms in pre-microRNAs with risk of ischemic stroke in a Chinese population.

Suli Huang,Yuebin Ke,Ziquan Lv,Shiquan Zhou,Tangchun Wu,Qian Zhang,Changhui Xie,Yanwei Zhang,Jinquan Cheng,Pingjian Deng,Ying Zhang,Yijie Geng,Shanshan Li,Xiaofan Chu,Zhaohui Yi

doi:10.1371/journal.pone.0117007

Abstract

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29–3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10–1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00–1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20–2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09–1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.

Highlights

Stroke is the second leading cause of death for people over 60 years old [1]
BMI, body mass index; FG, fasting glucose; TC, total cholesterol; TG, triglycerides; HDL-c, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. *Chi-square test for the difference in the distribution frequency between patients with ischemic stroke and control subjects. †Mann-Whitney U test for the differences between patients with ischemic stroke and control subjects
We evaluated the associations between two miRNA polymorphisms and the risk of ischemic stroke in a Chinese population, and estimated the gene-environment interaction and combined effects of miRNA polymorphisms and clinical characteristics

Summary

Introduction

Stroke is the second leading cause of death for people over 60 years old [1]. In China, with 1.4 billion populations, the annual stroke mortality rate is approximately 157 per 100000, which has exceeded heart disease and become the leading cause of death and adult disability [2]. In addition to the conventional risk factors, such as age, sex, body mass index, hypertension, diabetes mellitus, smoking, and hyperlipidemia, single-nucleotide polymorphisms (SNPs) have been identified in genome-wide association studies (GWAS) as susceptibility loci for ischemic stroke risk [4,5]. Such loci explain only a small portion of the total risk, and few of these SNPs discovered by GWAS involve miRNA genes

Methods

Results

Conclusion