Correlation of Differential Gene Expression and Clinical Variations in Hypertrophic Cardiomyopathy via Whole Genome Sequencing

Hypertrophic cardiomyopathy (HCM) is a prevalent cardiovascular disorder affecting populations worldwide, characterized by abnormal thickening of the heart muscle.(Supporting S1) The development of HCM is influenced by multiple factors, including genetic mutations, geographical conditions, lifestyle, and environmental exposures. The availability of extensive genomic datasets in public repositories provides an opportunity to identify potential genetic contributors and functional biomarkers associated with HCM. Previous studies have highlighted the pivotal role of the MYBPC3 gene in the pathogenesis of HCM. In this study, computational analyses were performed to predict gene mutations and functional biomarkers using RNA-sequencing and whole exome sequencing datasets. A total of 12 RNA-sequencing samples, comprising four healthy controls and eight HCM cases, along with 12 exome sequencing datasets, were retrieved from the Gene Expression Omnibus (GEO) database. RNA-sequencing analysis identified the top 20 differentially expressed genes associated with HCM, including MIB2, ZBTB48, MYBPC3, PRPF40B, CD27-AS1, MYH7, WDR90, KDM8, BCAM, ZSWIM9, KANK3, CCDC85A, ZNF512B, POLR3H, NUP210, PSMG4, GPLD1, GNL1, SH2D3C, and COL4A6. Among these, MYH7 exhibited the highest expression level, showing strong similarity to MYBPC3 in its association with HCM. Whole exome sequencing analysis further identified a panel of variant genes including MYBPC3, MYH6, MYH7, TNT, Titin, Desmin, ACE1, TGF-beta, Ang-2, SGCG, SGCA, DMD, and LaminA/C, all previously implicated in HCM pathophysiology. This integrative study underscores the correlation between differential gene expression patterns and clinical variants in HCM, providing valuable insights into the molecular mechanisms underlying the disease.