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

Abstract

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.

Human_SNP_TATAdb: a database of SNPs that statistically significantly change the affinity of the TATA-binding protein to human gene promoters: genome-wide analysis and use cases

“…This comparison was made to analyze whether these genes are under the influence of natural selection or neutral drift. We found that natural selection acts against underexpression of hub genes for atherogenesis, atherosclerosis and atheroprotection and, through enhanced atheroprotection, contributes to improved human health (Bogomolov et al, 2023).…”

“…Considering that to date quite a lot of studies have already been conducted in which this kind of annotation has been carried out, we will present the work (Bogomolov et al, 2023) as an example using the Human_SNP_TATAdb database for annotation and identification of candidate SNP markers of atherogenesis, atherosclerosis and atheroprotection.…”