Association of the genetic polymorphisms in immunoinflammatory microRNAs with risk of ischemic stroke and subtypes in an Iranian population

Stroke is one of the most common type of cerebrovascular disease threatening human health and life with high mortality, disability, and morbidity. Ischemic stroke (IS) is determined to be a complex disease containing a group of heterogeneous disorders with various environmental and genetic risk factors. This study evaluated the polymorphisms of microRNAs involved in inflammatory routes leading to stroke in an Iranian population. This study evaluated the associations of hsa-mir-608 C/G rs4919510, hsa-mir-499 A/G rs3746444, and hsa-mir-145 C/T rs190323149 polymorphisms in precursor miRNAs with the risk of IS. These microRNA polymorphisms were analyzed in 470 patients with IS and 489 control subjects. The TOAST criteria was applied for IS subtypes classification. The frequency of the allele G of hsa-mir-499/rs3746444 A/G revealed significant association with IS in comparison with controls (p<0.0001, OR=1.838, 95% CI=1.406-2.401). Increased IS risks were associated with hsa-mir-499/ rs3746444 A/G genotypes in diverse genetic model (homozygote comparison: p=0.004, OR=2.136, 95% CI=1.269-3.597; heterozygote comparison: p=0.029, OR=1.373, 95% CI=1.033-1.825). Statistical analysis in IS subtypes showed that cardio-embolic patients compared with other subtypes (large artery atherosclerosis and lacunar) had higher frequency of G allele (LAA vs. CEI, p=0.017; LAC vs. CEI, p=0.009), AG genotype (LAA vs. CEI, p=0.016; LAC vs. CEI, p=0.013). Nevertheless, this study did not find any association between the alleles and genotypes of mir-608 C/G rs4919510 SNP and IS, respectively (p>0.05). The current investigation provided verification that hsa-mir-499 rs3746444 A/G polymorphism may be associated with a significantly increased risk of IS in an Iranian population.