Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center (MGRC), Student Research Committee, Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Physiol. 2019 Apr;234(4):3874-3886. doi: 10.1002/jcp.27159. Epub 2018 Sep 19.
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.
中风是威胁人类健康和生命的最常见类型的脑血管疾病之一，其死亡率、残疾率和发病率都很高。缺血性中风（IS）被确定为一种复杂的疾病，包含一组具有不同环境和遗传风险因素的异质性疾病。本研究评估了与炎症途径相关的 microRNAs 多态性在伊朗人群中风中的作用。本研究评估了前体 microRNA 中 hsa-mir-608 C/G rs4919510、hsa-mir-499 A/G rs3746444 和 hsa-mir-145 C/T rs190323149 多态性与 IS 风险的关联。这些 microRNA 多态性在 470 名 IS 患者和 489 名对照中进行了分析。根据 TOAST 标准对 IS 亚型进行分类。与对照组相比，hsa-mir-499/rs3746444 A/G 的等位基因 G 的频率与 IS 显著相关（p<0.0001，OR=1.838，95%CI=1.406-2.401）。在各种遗传模型中，hsa-mir-499/ rs3746444 A/G 基因型与增加的 IS 风险相关（纯合子比较：p=0.004，OR=2.136，95%CI=1.269-3.597；杂合子比较：p=0.029，OR=1.373，95%CI=1.033-1.825）。在 IS 亚型中的统计分析表明，与其他亚型（大动脉粥样硬化和腔隙性）相比，心源性栓塞患者具有更高的 G 等位基因频率（LAA 与 CEI，p=0.017；LAC 与 CEI，p=0.009）、AG 基因型（LAA 与 CEI，p=0.016；LAC 与 CEI，p=0.013）。然而，本研究未发现 mir-608 C/G rs4919510 SNP 的等位基因和基因型与 IS 之间存在任何关联（p>0.05）。本研究结果验证了 hsa-mir-499 rs3746444 A/G 多态性可能与伊朗人群中风的显著增加风险相关。
