Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks

Non-alcoholic fatty liver disease (NAFLD) seems to have some molecular links with atherosclerosis (ATH); however, the molecular pathways which connect both pathologies remain unexplored to date. The identification of common factors is of great interest to explore some therapeutic strategies to improve the outcomes for those affected patients. Differentially expressed genes (DEGs) for NAFLD and ATH were extracted from the GSE89632 and GSE100927 datasets, and common up- and downregulated DEGs were identified. Subsequently, a protein-protein interaction (PPI) network based on the common DEGs was performed. Functional modules were identified, and the hub genes were extracted. Then, a Gene Ontology (GO) and pathway analysis of common DEGs was performed. DEGs analysis in NAFLD and ATH showed 21 genes that were regulated similarly in both pathologies. The common DEGs with high centrality scores were ADAMTS1 and CEBPA which appeared to be down- and up-regulated in both disorders, respectively. For the analysis of functional modules, two modules were identified. The first one was oriented to post-translational protein modification, where ADAMTS1 and ADAMTS4 were identified, and the second one mainly related to the immune response, where CSF3 was identified. These factors could be key proteins with an important role in the NAFLD/ATH axis.

Automated summary

Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (ATH) may share some molecular connections, but the underlying pathways have not been explored. This study aimed to identify common factors and potential therapeutic targets for both diseases. Differentially expressed genes (DEGs) were analyzed and common DEGs were identified. Protein-protein interaction (PPI) network analysis revealed functional modules and hub genes. Gene Ontology (GO) and pathway analysis were performed. The study found 21 genes with similar regulation in NAFLD and ATH. The hub genes ADAMTS1 and CEBPA were found to be down- and up-regulated, respectively. Functional modules related to protein modification and immune response were identified, with ADAMTS1, ADAMTS4, and CSF3 playing potential key roles.