Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling
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 expr...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ivan Kiselev Maxim Kozin Natalia Baulina Maria Pisklova Ludmila Danilova Alexandr Zotov Olga Chumakova Dmitry Zateyshchikov Olga Favorova |
| author_facet | Ivan Kiselev Maxim Kozin Natalia Baulina Maria Pisklova Ludmila Danilova Alexandr Zotov Olga Chumakova Dmitry Zateyshchikov Olga Favorova |
| author_sort | Ivan Kiselev |
| collection | DOAJ |
| description | 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 (<i>AUTS2</i>, <i>BRSK2</i>, <i>PRRT1</i>, and <i>SLC17A7</i>), 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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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:44:32Z |
| publishDate | 2022-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6b75a19631d5424fbd82dc5513da2c3a2023-11-24T11:16:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231528010.3390/ijms232315280Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome ProfilingIvan Kiselev0Maxim Kozin1Natalia Baulina2Maria Pisklova3Ludmila Danilova4Alexandr Zotov5Olga Chumakova6Dmitry Zateyshchikov7Olga Favorova8E.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaJohns Hopkins School of Medicine, Baltimore, MD 21205, USAE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaE.I. Chazov National Medical Research Center for Cardiology, Moscow 121552, RussiaHypertrophic 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 (<i>AUTS2</i>, <i>BRSK2</i>, <i>PRRT1</i>, and <i>SLC17A7</i>), 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.https://www.mdpi.com/1422-0067/23/23/15280hypertrophic cardiomyopathygene expressiontranscriptomeDNA methylationmethylomepathway analysis |
| spellingShingle | Ivan Kiselev Maxim Kozin Natalia Baulina Maria Pisklova Ludmila Danilova Alexandr Zotov Olga Chumakova Dmitry Zateyshchikov Olga Favorova Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling International Journal of Molecular Sciences hypertrophic cardiomyopathy gene expression transcriptome DNA methylation methylome pathway analysis |
| title | Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling |
| title_full | Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling |
| title_fullStr | Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling |
| title_full_unstemmed | Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling |
| title_short | Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling |
| title_sort | novel genes involved in hypertrophic cardiomyopathy data of transcriptome and methylome profiling |
| topic | hypertrophic cardiomyopathy gene expression transcriptome DNA methylation methylome pathway analysis |
| url | https://www.mdpi.com/1422-0067/23/23/15280 |
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