Association of miR-196a2 and miR-149 single-nucleotide polymorphisms with atherosclerotic ischemic stroke susceptibility

Abstract

Background: Beside common risk factors for stroke such as diabetes and hypertension, single-nucleotide variants occurring within micro RNA genes have been identified as susceptibility loci for ischemic stroke risk. Objectives: Investigate the possible association of two variants in pre miRNA sequences, rs11614913 within miR-196a2 C > T and rs2292832 within miR-149 T > C, with ischemic stroke. Subjects and methods: One hundred ischemic stroke patients and 100 age and sex-matched controls having > 1 risk factor for atherosclerosis were enrolled in a case-control study. Degree of atherosclerosis was assessed using ultrasonography. Micro RNA variants were assessed by real-time PCR TaqMan probe assay. Results: The TT genotype and T allele frequencies of miR-196a2 C > T were protective against ischemic stroke (OR 0.168, P 0.001; OR 0.482, P < 0.001 respectively). While among miR-149 T > C variants, CC genotype was associated with increased risk by threefold (OR 3.061, P 0.005) and C allele was associated with about 1.9 fold risk of stroke (OR 1.909, P 0.002). Haplotypes analysis revealed miR-196a2T/-149 T allele combination was significantly lower among stroke patients than the controls (P < 0.001) with a protective effect (OR 0.196, 95% CI 0.083-0.466). Conclusion: A decrease in the incidence of ischemic stroke is associated with miR-196a2 TT genotype and T allele and increases in the likelihood risk of ischemic stroke are associated with CC genotype and C allele within miR-149, and the two miRNAs under study are closely associated with vascular damage responses.