Key genes and pathogenesis related to type 2 diabetes and cardiogenic stroke

与2型糖尿病和心源性卒中相关的关键基因和发病机制

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Abstract

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.

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