Accepted_test

Candidate SNP markers significantly altering the affinity of TATA-binding protein for the promoters of human hub genes for atherogenesis, atherosclerosis and atheroprotection
by Tverdokhleb N. | Chadaeva I. | Filonov S. | Zolotareva K. | Podkolodnyy N. | Khandaev B. | Rasskazov D. | Bogomolov A. | Kazachek A. | Oshchepkov D. | Ivanisenko V. | Demenkov P. | Podkolodnaya O. | Ponomarenko P. | Mustafin Z. | Kondratyuk E. | Savinkova L. | Ponomarenko M. | Suslov V. | Kolchanov N. | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Novosibirsk State University, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia
Abstract ID: 122
Event: BGRS-abstracts
Sections: [Sym 1] Section “Genome-wide transcriptomics (differential gene expression)”

Motivation and Aim: Atherosclerosis is a systemic disease in which focal lesions in arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development of atheroma (atherogenesis) narrows blood vessels, reduces the blood supply and leads to cardiovascular diseases. According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death, which has been especially boosted since the COVID-19 pandemic. There is a variety of contributors to atherosclerosis, including lifestyle factors and genetic predisposition. Antioxidant diets and recreational exercises act as atheroprotectors and can retard atherogenesis. The search for molecular markers of atherogenesis and atheroprotection for predictive, preventive and personalized medicine appears to be the most promising direction for the study of atherosclerosis.

Methods and Algorithms: Here, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection [1], as depicted in the Figure.

Results: The hub genes regulating these processes have been found to be the most ancient by means of the an in silico phylostratigraphic analysis [2, 3]. In silico analysis using our freely available web service SNP_TATA_Comparator [4] of all 5112 SNPs in their promoters has revealed 330 candidate SNP markers, which statistically significantly change the affinity of the TATA-binding protein (TBP) for these promoters, as shown in the Table 1.

Conclusion: These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection, while upregulation of the only atheroprotection-related genes promotes human health according to the Table 2.