Candidate SNP Markers of Atherogenesis Significantly Shifting the Affinity of TATA-Binding Protein for Human Gene Promoters show stabilizing Natural Selection as a Sum of Neutral Drift Accelerating Atherogenesis and Directional Natural Selection Slowing It

Autor: Evgeniya Oshchepkova, Dmitry Oshchepkov, I. A. Drachkova, Mikhail P. Ponomarenko, Ekaterina Sharypova, M.S. Nazarenko, P. M. Ponomarenko, D. A. Rasskazov, Irina Chadaeva, Ludmila Savinkova, Nikolay A. Kolchanov
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
single nucleotide polymorphism (snp)
030204 cardiovascular system & hematology
lcsh:Chemistry
0302 clinical medicine
TATA-binding protein (TBP) TBP-binding site (TATA box)
single nucleotide polymorphism (SNP)
candidate SNP marker
Stabilizing selection
Promoter Regions
Genetic
lcsh:QH301-705.5
Spectroscopy
Genetics
Pancreatic Elastase
General Medicine
TATA Box
Computer Science Applications
Genetic Markers
dbSNP
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
Article
Catalysis
Autoimmune Diseases
Inorganic Chemistry
03 medical and health sciences
tata-binding protein (tbp) tbp-binding site (tata box)
Matrix Metalloproteinase 12
Humans
SNP
Genetic Predisposition to Disease
human
Selection
Genetic
Physical and Theoretical Chemistry
gene
Molecular Biology
Gene
promoter
Macrophages
Organic Chemistry
Promoter
TATA-Box Binding Protein
candidate snp marker
verification in vitro
MicroRNAs
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Genome
Mitochondrial
biology.protein
Human genome
TATA-binding protein
atherosclerosis
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 3
International Journal of Molecular Sciences, Vol 21, Iss 3, p 1045 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21031045
Popis: (1) Background: The World Health Organization (WHO) regards atherosclerosis-related myocardial infarction and stroke as the main causes of death in humans. Susceptibility to atherogenesis-associated diseases is caused by single-nucleotide polymorphisms (SNPs). (2) Methods: Using our previously developed public web-service SNP_TATA_Comparator, we estimated statistical significance of the SNP-caused alterations in TATA-binding protein (TBP) binding affinity for 70 bp proximal promoter regions of the human genes clinically associated with diseases syntonic or dystonic with atherogenesis. Additionally, we did the same for several genes related to the maintenance of mitochondrial genome integrity, according to present-day active research aimed at retarding atherogenesis. (3) Results: In dbSNP, we found 1186 SNPs altering such affinity to the same extent as clinical SNP markers do (as estimated). Particularly, clinical SNP marker rs2276109 can prevent autoimmune diseases via reduced TBP affinity for the human MMP12 gene promoter and therefore macrophage elastase deficiency, which is a well-known physiological marker of accelerated atherogenesis that could be retarded nutritionally using dairy fermented by lactobacilli. (4) Conclusions: Our results uncovered SNPs near clinical SNP markers as the basis of neutral drift accelerating atherogenesis and SNPs of genes encoding proteins related to mitochondrial genome integrity and microRNA genes associated with instability of the atherosclerotic plaque as a basis of directional natural selection slowing atherogenesis. Their sum may be stabilizing the natural selection that sets the normal level of atherogenesis.
Databáze: OpenAIRE
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