Bioinformatics analysis of sex differences in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease that exhibits sex differences on clinical presentation. The present study aimed to investigate the sex differences associated with ARVC by conducting an integrated bioinformatics analysis. The GSE29819 gene expression dataset was downloaded from the Gene Expression Omnibus database. The online analytical tool GEO2R was then used to screen for differentially expressed genes (DEGs), which were subsequently processed using enrichment analysis and protein-protein interaction (PPI) network construction. Functional annotation of the DEGs was determined using ClueGO. The PPI network was constructed with Search Tool for the Retrieval of Interacting Genes, and was visualized with Cytoscape to identify the modules and hub genes. Compared with the female group, a total of 1,188 DEGs, of which 915 were upregulated and 273 were downregulated, were identified in the male group. The enrichment analysis revealed that in KEGG pathways, the upregulated DEGs were substantially enriched in the ‘nicotine addiction’ pathways, whereas the downregulated DEGS were mainly enriched in the ‘ECM-receptor interaction’ and ‘protein digestion and absorption’ pathways. The PPI network contained 899 nodes and 1,627 edges, among which four significant modules were identified. In addition, kininogen 1, lysophosphatidic acid receptor 5, formyl peptide receptor (FPR) 2, adenylate cyclase 2, γ-aminobutyric acid type B receptor subunit 2, FPR1, hydroxycarboxylic acid receptor 1, prostaglandin E receptor 3, cannabinoid receptor 1 and proenkephalin were identified as the top 10 hub genes. The key genes and related pathways identified in this study provide genetic insight into the diversity in phenotypes between female and male patients with ARVC, and may facilitate therapeutic individualization.