Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling
2022
Ivan Kiselev | Maxim Kozin | Natalia Baulina | Maria Pisklova | Ludmila Danilova | Alexandr Zotov | Olga Chumakova | Dmitry Zateyshchikov | Olga Favorova
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease: its pathogenesis is still being intensively studied to explain the reasons for the significant genetic and phenotypic heterogeneity of the disease. To search for new genes involved in HCM development, we analyzed gene expression profiles coupled with DNA methylation profiles in the hypertrophied myocardia of HCM patients. The transcriptome analysis identified significant differences in the 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. 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 common genes, the expressions of which correlated with the methylation levels of the neighboring DMPs. Half of these genes (AUTS2, BRSK2, PRRT1, and SLC17A7), regulated by the mechanism of DNA methylation, were underexpressed in HCM and were involved in neurogenesis and synapse functioning. Our data, suggesting the involvement of innervation-associated genes in HCM, provide additional insights into disease pathogenesis and expand the field of further research.
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