Identification and Analysis of Pivotal Genes in Type 2 Diabetes Mellitus Combined With Non-Alcoholic Fatty Liver Disease

Abstract

Abstract Objective Type 2 diabetes combined with non-alcoholic fatty liver disease (NAFLD) rapidly increases the risk of developing cirrhosis or even liver failure in type 2 diabetes, and no drugs have yet emerged to specifically treat this disease. Therefore, it is urgent to find the precise targets for the pathogenesis of type 2 diabetes combined with NAFLD. Thus, this paper uses bioinformatics to analyze the candidate genes involved in diabetes combined with NAFLD and their potential mechanisms. Methods GSE49541 was downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) associated with NAFLD.The DEGs were intersected with the three major metabolism-related genes, and the co-expressed DEGs were subjected to functional enrichment analysis and WGCNA (Weighted Gene Co-Expression Network Analysis) analysis to construct modules closely related to NAFLD in T2DM, thereby screening the target modules for genes and lncRNAs that were significantly enriched,and constructing lncRNA and mRNA co-expression networks related to the metabolism of the three substances. In the Comparative Toxicogenomics Database (CTD), we obtained genes and pathways directly related to NAFLD and T2DM, constructed disease pathways involved in NAFLD and T2DM disease genes, and combined with GSEA analysis to screen out core genes, related lncRNAs and key pathways. Results A total of 641 DERs were obtained by differential analysis, and 251 overlapping gene DEGs were obtained by taking intersections in the three major metabolisms, which were analyzed by GO and KEGG enrichment, and these overlapping DEGs were involved in 666 GO analysis and 44 KEGG enrichment analysis results. They were mainly associated with metabolic processes such as lipid metabolism, fatty acid metabolism and amino acid metabolism, PPAR signalling pathway, ketone body synthesis and degradation. The 25 hub genes in the brown module and the 96 hub genes in the turquois module were obtained by WGCNA analysis, respectively. Finally, by constructing a lncRNA-mRNA-KEGG co-expression network, four disease genes (AHCY, PEMT,CYP2E1, GNMT) were obtained as possible candidate biomarkers for type 2 diabetes combined with NAFLD. Six lncRNAs associated with disease genes were also obtained: RAB11B-AS1, LINC01018, LINC01806, LINC00844, NNT-AS1, LINC01128. Conclusion The pathogenesis and progression of type 2 diabetes mellitus combined with non-alcoholic fatty liver disease is caused by multiple pathways, which also provides clinicians with potential therapeutic tools for its treatment.