Hypertrophic cardiomyopathy: data of transcriptome profiling and epigenome-wide DNA methylation analysis

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, and its pathogenesis is still being intensively studied to explain the reasons of significant genetic and phenotypic heterogeneity of the disease. To search for possible HCM modifier genes involved in the HCM development we first attempted to analyze gene expression profile coupled with DNA methylation profile in the hypertrophied myocardium of HCM patients; the control group consisted of patients with aortic stenosis. The transcriptome analysis identified significant differences in levels of 193 genes, most of which were underexpressed in HCM. The methylome analysis revealed 1755 nominally significant differentially methylated positions (DMPs), mostly hypomethylated in HCM. The clear differences in DNA methylation profiles between the studied groups indicate the involvement of this process in the formation of primary left ventricle hypertrophy in HCM. Based on gene ontology enrichment analysis, the majority of biological processes, overrepresented by both differentially expressed genes (DEGs) and DMP-containing genes, are involved in the regulation of locomotion and muscle structure development. The intersection of 193 DEGs and 978 DMP-containing genes pinpointed eight genes, expression of which differed between studied groups and correlated with methylation levels of the neighboring DMPs. Half of these genes (AUTS2, GIGYF1, PRRT1, and SLC17A7) were found underexpressed in HCM and involved in neurogenesis and synapse functioning. Our data suggesting the possible involvement of innervation-associated genes in HCM provide additional insights in the disease pathogenesis and expand the field of further research. We performed RNA-seq analysis of the heart left ventricle samples obtained from 8 patients with hypertrophic cardiomyopathy and 5 samples from patients with aortic stenosis.