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微小 RNA 生物发生基因多态性与大动脉粥样硬化性脑卒中风险的关联。

Association of MicroRNA Biogenesis Genes Polymorphisms with Risk of Large Artery Atherosclerosis Stroke.

机构信息

Department of Neurology, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.

Department of Neurology, The Third Affiliated Hospital of Soochow University, Changzhou, China.

出版信息

Cell Mol Neurobiol. 2022 Aug;42(6):1801-1807. doi: 10.1007/s10571-021-01057-8. Epub 2021 Feb 23.

Abstract

Convincing evidence has shown that microRNAs (miRNAs) are involved in the pathogenesis of stroke. This study aimed to examine whether miRNA biogenesis genes polymorphisms are associated with risk of large artery atherosclerosis (LAA) stroke. Three polymorphisms (DROSHA rs10719 T>C, RAN rs3803012 A>G, and PIWIL1 rs10773771 C>T) were screened by certain criteria. A total of 1,785 (710 cases and 1,075 controls) study subjects were included in this study. We found that rs10773771 CC genotype was associated with a decreased risk of LAA stroke (CC vs. TT/CT: OR 0.63, 95% CI 0.46-0.86, P = 3 × 10). In silico analysis suggested that rs10773771 can change the mRNA secondary structure of PIWIL1 and affect the binding of the miRNAs and regulatory motifs to the 3'-UTR of PIWIL1. Expression quantitative trait loci analysis showed that rs10773771 could change the expression of PIWIL1 in human skin (P = 1.534 × 10) and thyroid tissues (P = 4.869 × 10). These findings suggested that PIWIL1 rs10773771 may be associated with a decreased risk of LAA stroke.

摘要

有充分证据表明 microRNAs(miRNAs)参与了中风的发病机制。本研究旨在探讨 miRNA 生物发生基因多态性是否与大动脉粥样硬化(LAA)性中风的风险相关。通过特定标准筛选了三个多态性(DROSHA rs10719 T>C、RAN rs3803012 A>G 和 PIWIL1 rs10773771 C>T)。本研究共纳入了 1785 名研究对象(710 例病例和 1075 例对照)。我们发现 rs10773771 CC 基因型与 LAA 中风风险降低相关(CC 与 TT/CT:OR 0.63,95%CI 0.46-0.86,P=3×10)。计算机分析表明,rs10773771 可以改变 PIWIL1 的 mRNA 二级结构并影响 miRNA 和调控元件与 PIWIL1 3'-UTR 的结合。表达数量性状基因座分析表明,rs10773771 可以改变人皮肤(P=1.534×10)和甲状腺组织中 PIWIL1 的表达(P=4.869×10)。这些发现表明,PIWIL1 rs10773771 可能与 LAA 中风风险降低相关。

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