Wang Yu-Ye, Zhang He-Yu, Jiang Wen-Juan, Liu Fang, Li Lei, Deng Shu-Min, He Zhi-Yi, Wang Yan-Zhe
Department of Neurology, Key Laboratory for Neurological Big Data of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2021 Jul;16(7):1302-1307. doi: 10.4103/1673-5374.301019.
Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms. Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke. Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs. In this case-control study, we analyzed the distribution of pri-let-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors. Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University. We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke. Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample. We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension. Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk. This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China (approval No. 2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559) on December 27, 2017.
缺血性中风是一种复杂的疾病，其发病机制归因于基因多态性的出现。有证据表明，微小RNA let-7a参与缺血性中风的发病机制。初级微小RNA（pri-miRNA）是初级转录本，它经过几个加工步骤生成前体微小RNA（pre-miRNA），随后生成成熟的微小RNA。在这项病例对照研究中，我们分析了pri-let-7a-2变体在缺血性中风高危患者中的分布以及pri-let-7a-2变体与环境因素的相互作用。2013年12月至2015年12月期间，在中国医科大学附属第一医院收集了1086例缺血性中风患者和836例健康对照者的血液样本及临床信息。我们发现，rs1143770的CC基因型和C等位基因与缺血性中风风险降低相关，而rs629367的CC基因型与缺血性中风风险增加相关。此外，在本研究样本中，这两个单核苷酸多态性处于连锁不平衡状态。我们分析了基因-环境相互作用，发现rs1143770与饮酒、吸烟和高血压病史共同对缺血性中风的发病机制产生联合作用。因此，检测pri-let-7a-2多态性可能会提高对缺血性中风风险的认识。本研究于2012年2月20日获得中国医科大学附属第一医院机构伦理委员会批准（批准号：2012 - 38 - 1），并于2017年12月27日在中国临床试验注册中心注册（注册号：ChiCTR - COC - 17013559）。
