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Methylation of Regulatory Regions of DNA Repair Genes in Carotid Atherosclerosis

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Abstract

The status of DNA methylation in the human genome changes during the pathogenesis of common diseases and acts as a predictor of life expectancy. Therefore, it is of interest to investigate the methylation level of regulatory regions of genes responsible for general biological processes that are potentially significant for the development of age-associated diseases. Among them there are genes encoding proteins of DNA repair system, which are characterized by pleiotropic effects. Here, results of the targeted methylation analysis of two regions of the human genome (the promoter of the MLH1 gene and the enhancer near the ATM gene) in different tissues of patients with carotid atherosclerosis are present. Analysis of the methylation profiles of studied genes in various tissues of the same individuals demonstrated marked differences between leukocytes and tissues of the vascular wall. Differences in methylation levels between normal and atherosclerotic tissues of the carotid arteries were revealed only for two studied CpG sites (chr11:108089866 and chr11:108090020, GRCh37/hg19 assembly) in the ATM gene. Based on this, we can assume the involvement of ATM in the development of atherosclerosis. “Overload” of the studied regions with transcription factor binding sites (according to ReMapp2022 data) indicate that the tissue-specific nature of methylation of the regulatory regions of the MLH1 and ATM may be associated with expression levels of these genes in a particular tissue. It has been shown that inter-individual differences in the methylation levels of CpG sites are associated with sufficiently distant nucleotide substitutions.

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ACKNOWLEDGMENTS

We are grateful to Cand. Sci. (Med.) A.V. Markov for help in experiment planning and preparation.

The study was performed using equipment of the Medical Genomics Collective Access Center (Tomsk National Research Medical Center) and the Biobank of the North Eurasian Population (Research Institute of Medical Genetics, Tomsk National Research Medical Center).

Funding

This work was supported by the Ministry of Science and Higher Education (project no. 122020300041-7).

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  1. Institute of Medical Genetic, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050, Tomsk, Russia

    N. P. Babushkina, A. A. Zarubin, Iu. A. Koroleva, D. E. Gomboeva, E. Yu. Bragina, I. A. Goncharova, M. V. Golubenko, R. R. Salakhov, A. A. Sleptcov, A. N. Kucher & M. S. Nazarenko

  2. Institute of Cardiology, Tomsk National Research Medical Center, Russian Academy of Sciences, 634034, Tomsk, Russia

    M. S. Kuznetsov, B. N. Kozlov, E. F. Muslimova & S. A. Afanasiev

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study. The study has been approved by the Ethics Committee at the Institute of Medical Genetics (protocol no. 10 dated February 15, 2021).

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Babushkina, N.P., Zarubin, A.A., Koroleva, I.A. et al. Methylation of Regulatory Regions of DNA Repair Genes in Carotid Atherosclerosis. Mol Biol 57, 637–652 (2023). https://doi.org/10.1134/S0026893323040027

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