Methylation of Regulatory Regions of DNA Repair System Genes in Carotid Atherosclerosis

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

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.

Негізгі сөздер

Авторлар туралы

N. Babushkina

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

A. Zarubin

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

Iu. Koroleva

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

D. Gomboeva

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

E. Bragina

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

I. Goncharova

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

M. Golubenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

R. Salakhov

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

A. Sleptcsov

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

M. Kuznetsov

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634034, Tomsk

B. Kozlov

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634034, Tomsk

E. Muslimova

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634034, Tomsk

S. Afanasiev

Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634034, Tomsk

A. Kucher

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

M. Nazarenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Email: nad.babushkina@medgenetics.ru
Russia, 634050, Tomsk

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© Н.П. Бабушкина, А.А. Зарубин, Ю.А. Королёва, Д.Е. Гомбоева, Е.Ю. Брагина, И.А. Гончарова, М.В. Голубенко, Р.Р. Салахов, А.А. Слепцов, М.С. Кузнецов, Б.Н. Козлов, Э.Ф. Муслимова, С.А. Афанасьев, А.Н. Кучер, М.С. Назаренко, 2023

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