Comprehensive bioinformatics analysis identifies specific female genetics for HCM with a higher cardiovascular risk

Abstract Background The study was conducted to identify specific gene expressions and mostly associated mechanisms of sex differences in hypertrophic cardiomyopathy (HCM). Methods and results The differential expressed genes (DEGs) and biological functions were analyzed. Furthermore, LASSO model, combined with SVM-RFE feature was applied for core genes. GO terms and gene set enrichment analysis (GSEA) were conducted. Core genes and related mechanisms were verified in male to tell the sex differences in genetics. There revealed seven core genes, i.e., ZFP36, CEBPD, S100A9, CDC42EP4, RASD1, S1PR3, and MYH6 , with a significant decrease in HCM females. GSEA indicated there existed signaling pathways including fatty acid β-oxidation, tricarboxylic acid cycle enzyme complex, autophagy, and ribosome pathways involved in low expressions of these genes in female-specific HCM. Also, core gene expressions were verified in male-specific HCM, indicating more reduction of RASD1 and MYH6 in HCM females than males. As to autophagy-related signatures, expression levels of NAMPT decreased significantly in HCM women, with sex differences, meanwhile there presented a significantly positive correlation between NAMPT with RASD1 (R=0.557, p <0.001) or MYH6 (R=0.516, p <0.001). Conclusions The comprehensive bioinformatic analyses indicated that low RASD1/MYH6/NAMPT expressions in cardiac tissues of females were closely related to HCM with a higher risk of cardiovascular events.