TY - JOUR

T1 - Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection

AU - Bogomolov, Anton

AU - Filonov, Sergey

AU - Chadaeva, Irina

AU - Rasskazov, Dmitry

AU - Khandaev, Bato

AU - Zolotareva, Karina

AU - Kazachek, Anna

AU - Oshchepkov, Dmitry

AU - Ivanisenko, Vladimir A

AU - Demenkov, Pavel

AU - Podkolodnyy, Nikolay

AU - Kondratyuk, Ekaterina

AU - Ponomarenko, Petr

AU - Podkolodnaya, Olga

AU - Mustafin, Zakhar

AU - Savinkova, Ludmila

AU - Kolchanov, Nikolay

AU - Tverdokhleb, Natalya

AU - Ponomarenko, Mikhail

N1 - Funding: This study was supported by the Russian Federal Science and Technology Program for the Development of Genetic Technologies. We are thankful to the multi-access bioinformatics center for the use of computational resources as supported by Russian government project No. FWNR-2022-0020

PY - 2023/5/19

Y1 - 2023/5/19

N2 - 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. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis 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. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.

AB - 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. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis 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. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.

KW - Humans

KW - TATA-Box Binding Protein/genetics

KW - Polymorphism, Single Nucleotide

KW - Cardiovascular Diseases/genetics

KW - Pandemics

KW - COVID-19/genetics

KW - Atherosclerosis/genetics

KW - TATA Box

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85160377000&origin=inward&txGid=f0fd259111c01206fd2a1bb8dc0d4a49

U2 - 10.3390/ijms24109010

DO - 10.3390/ijms24109010

M3 - Article

C2 - 37240358

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 10

M1 - 9010

ER -