Candidate SNP Markers of Atherosclerosis That May Significantly Change the Affinity of the TATA-Binding Protein for the Human Gene Promoters

M. P. Ponomarenko, D. A. Rasskazov, I. V. Chadaeva, E. B. Sharypova, I. A. Drachkova, P. M. Ponomarenko, E. A. Oshchepkova, L. K. Savinkova, N. A. Kolchanov

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Atherosclerosis (AS) and AS-related pathologies such as coronary heart disease, myocardial infarction, angina pectoris, and stroke are the leading causes of death in the world. The atherogenesis can be influenced by many factors, in particular, overweight, hypertension, diabetes, hyperlipoproteinemia, and other diseases in anamnesis, as well as genetic predisposition, which may be due to single nucleotide polymorphisms (SNPs) in some cases. In this work, we studied only those regions of promoters of the human protein-coding genes where SNP markers of changes in the affinity of the TATA-binding protein (TBP) for these promoters have already been associated with the atherosclerosis-related pathologies. As a result, within the dbSNP database, we found those unannotated SNPs which change such affinity just as the known biomedical SNP markers do here (according to the predictions made by our Web service SNP_TATA_Z-tester, http://wwwmgs.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl). For example, the known SNP marker rs35036378 of the high risks of the primary pT1 tumor reduces the TBP affinity for the ESR2 gene promoter and, thus, the estrogen receptor β abundancy in blood, which is a known physiological marker of calcification of blood vessels in atherogenesis. Near this known SNP marker, we found an unannotated SNP rs766797386, which can also reduce the TBP affinity for the same promoter and, thus, decrease the abundance of the estrogen receptor β in blood. Thus, we propose rs766797386 as a candidate SNP marker for accelerated atherogenesis due to calcification of blood vessels. The possibility of using a diet of natural food with high abundance of calcium (Ca), which is recommended by nutritionists to slow down calcification in the case when individuals have SNP markers of accelerated calcification, is discussed in contrast to the use of Ca-enriched nutritional supplements that can cause the opposite effect. In the same way, a total of 33 candidate SNP markers were predicted and discussed to accelerate or slow down atherogenesis. After clinical verification, the candidate SNP markers predicted by this work can help those who would like to slow down atherogenesis through lifestyle corrections using their genome sequencing data.

Original languageEnglish
Pages (from-to)1137-1151
Number of pages15
JournalRussian Journal of Genetics
Volume55
Issue number9
DOIs
Publication statusPublished - 1 Sep 2019

Keywords

  • atherosclerosis
  • promoter
  • single nucleotide polymorphism (SNP)
  • TATA-binding protein (TBP)
  • TBP-binding site (TATA box)
  • MATRIX METALLOPROTEINASE-12
  • BOX POLYMORPHISMS
  • TRANSCRIPTION
  • DEFICIENCY
  • HUMAN HEREDITARY-DISEASES
  • DNA
  • NITRIC-OXIDE
  • CELL
  • EXPRESSION
  • PROGRESSION

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