DIFFERENTIAL METHYLATION OF THE GENES PAX8 AND GATA4 ALTERS THEIR EXPRESSION IN THE HEART DURING HYPERTROPHIC CARDIOMYOPATHY

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Abstract

Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease with a prevalence ranging from 1:500 to 1:200 individuals. The development and clinical presentation of HCM do not always conform to the traditional view of its monogenic inheritance pattern. One key to addressing this issue may lie in identifying epigenetic mechanisms regulating gene expression, particularly DNA methylation, involved in the pathogenesis of the disease and modifying its course. Utilizing previously obtained whole-genome data, we identified four extended genomic regions with reduced methylation levels in the myocardium of patients with HCM. These include region chr2:113993204-113994075 located within the transcribed area of the PAX8 gene, as well as three other regions – chr6:31148369-31148577, chr8:11565217-11567212, and chr8:22132791-22133357 – that are associated with promoters of genes PSORS1C3, GATA4, and PIWIL2, respectively. We were able to demonstrate altered expression of PAX8 and GATA4 genes containing one each of these four mentioned regions. Our findings will expand the currently very limited understanding of the unique features of epigenetic regulation in this condition.

About the authors

I. S Kiselev

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Email: kiselev.ivan.1991@gmail.com
Moscow, Russian Federation

E. A Dashtieva

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

M. V Pisklova

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

O. S Chumakova

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

A. S Zotov

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

M. R Kabilov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russian Federation

O. A Baturina

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russian Federation

D. A Zateyshchikov

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

O. O Favorova

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

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