[Methylation of Regulatory Regions of DNA Repair Genes in Carotid Atherosclerosis].

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  • Additional Information
    • Source:
      Publisher: Izdatelstvo Nauka Country of Publication: Russia (Federation) NLM ID: 0105454 Publication Model: Print Cited Medium: Print ISSN: 0026-8984 (Print) Linking ISSN: 00268984 NLM ISO Abbreviation: Mol Biol (Mosk) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Moskva : Izdatelstvo Nauka
    • Subject Terms:
      Atherosclerosis*/genetics ; Atherosclerosis*/metabolism ; Atherosclerosis*/pathology ; Carotid Artery Diseases*/genetics; Humans ; CpG Islands/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; DNA Methylation ; DNA Repair/genetics
    • 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.
    • Contributed Indexing:
      Keywords: ATM gene; CpG islands; DNA methylation; MLH1 gene; Next Generation sequencing (NGS); atherosclerosis
    • Publication Date:
      Date Created: 20230802 Date Completed: 20231102 Latest Revision: 20231102
    • Publication Date:
      20231102
    • Accession Number:
      10.31857/S002689842304002X, EDN: QKQNQS
    • Accession Number:
      37528784