Identification of Key Genes and Pathways in Hypertrophic Cardiomyopathy via Weighted Gene Co-Expression Network Analysis

Abstract

BackgroundHypertrophic cardiomyopathy (HCM) is a prevalent cardiovascular disease characterized as asymmetric hypertrophy of ventricular muscles. Cardiac morphological abnormality may result in slight or severe cardiopulmonary symptoms, arrhythmia, heart failure, and even sudden death. Previous studies have shown that HCM was an inherited disease where sixty percent carry mutations in genes encoding sarcomere proteins. However, considering heterogeneous phenotype or prognosis, the underlying mechanisms remain unclear.MethodsThe gene expression profiles of GSE36961 and GSE160997 were analyzed by ‘limma’ and ‘weighted gene co-expression network analysis (WGCNA)’ package in R to identify differentially expressed genes (DEGs) and key modules, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Protein-protein interaction network was constructed based on the overlapped genes of DEGs and key modules, and we identified the top 4 hub genes using ‘cytohubba’ according to inner connectivity.ResultsWe identified the red and brown modules as the key modules. Enrichment analysis showed that cellular divalent inorganic cation homeostasis, collagen−containing extracellular matrix, and actin binding were significantly enriched. VSIG4, CD163, FCER1G, and LAPTM5 were identified as hub genes.ConclusionsThis study suggested that VSIG4, CD163, FCER1G, and LAPTM5 might be hub genes associated with the progression of HCM. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.