Deng Zhiyuan, Wang Manjia, Song Hongli, Liu Min
Department of Endocrinology, Gaozhou Hospital of Traditional Chinese Medicine, Gaozhou, China.
Department of Gynecology, Gaozhou Hospital of Traditional Chinese Medicine, Gaozhou, China.
Medicine (Baltimore). 2025 Sep 5;104(36):e44242. doi: 10.1097/MD.0000000000044242.
Type 2 diabetes mellitus (T2DM) and cardiogenic stroke (CS) are harmful to human health. Previous studies have shown a correlation between T2DM and CS, but the causal relationships and pathogenic mechanisms between T2DM and CS remain unclear. We downloaded T2DM and CS datasets from a genome-wide Association Study and performed Mendelian randomization (MR) analysis using the TwoSampleMR package in R software. To obtain differentially expressed genes, The Limma package of R software was used to analyze the T2DM and CS datasets. Both datasets were acquired from the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to analyze co-driver genes for pathway enrichment. On the basis of protein-protein interaction network and Interaction Gene Retrieval Tool database, the hub genes were founded using Cytoscape software. The regulatory relationship between microRNAs (miRNAs) and hub genes was demonstrated using NetworkAnalyst. The Cytoscape plugin, CytoHubba tool, was employed to screen hub genes and evaluate common diagnostic markers for T2DM and CS. The MR analysis showed a correlation between T2DM and CS. T2DM increased the risk of CS (P = .003, inverse-variance weighted method). There was no statistical heterogeneity among single nucleotide polymorphisms strongly associated with T2DM (Cochran's Q = 130.48, P = .139) and no horizontal pleiotropy among single nucleotide polymorphisms strongly associated with T2DM (P = .677, MR-Egger regression). We predicted that miR-34a-5p, miR-103-3p, miR-107, and miR-124-3p may be key miRNAs in the miRNA-gene network. This study suggested that T2DM increased the risk of CS, and T2DM and CS share common diagnostic biomarkers and pathogenic pathways.
2型糖尿病（T2DM）和心源性卒中（CS）对人类健康有害。先前的研究表明T2DM与CS之间存在相关性，但T2DM与CS之间的因果关系和致病机制仍不清楚。我们从全基因组关联研究中下载了T2DM和CS数据集，并使用R软件中的TwoSampleMR包进行孟德尔随机化（MR）分析。为了获得差异表达基因，使用R软件的Limma包分析T2DM和CS数据集。两个数据集均从基因表达综合数据库获取。基因本体论和京都基因与基因组百科全书用于分析共驱动基因的通路富集情况。基于蛋白质-蛋白质相互作用网络和相互作用基因检索工具数据库，使用Cytoscape软件确定枢纽基因。使用NetworkAnalyst证明了微小RNA（miRNA）与枢纽基因之间的调控关系。使用Cytoscape插件CytoHubba工具筛选枢纽基因并评估T2DM和CS的常见诊断标志物。MR分析显示T2DM与CS之间存在相关性。T2DM增加了CS的风险（P = 0.003，逆方差加权法）。与T2DM强烈相关的单核苷酸多态性之间无统计学异质性（ Cochr an's Q = 130.48，P = 0.139），与T2DM强烈相关的单核苷酸多态性之间无水平多效性（P = 0.677，MR-Egger回归）。我们预测miR-34a-5p、miR-103-3p、miR-107和miR-124-3p可能是miRNA-基因网络中的关键miRNA。本研究表明，T2DM增加了CS的风险，且T2DM和CS共享常见的诊断生物标志物和致病途径。
