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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. / Ponomarenko, Mikhail; Rasskazov, Dmitry; Chadaeva, Irina et al.
In: International Journal of Molecular Sciences, Vol. 21, No. 3, 1045, 05.02.2020.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - 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
AU - Ponomarenko, Mikhail
AU - Rasskazov, Dmitry
AU - Chadaeva, Irina
AU - Sharypova, Ekaterina
AU - Drachkova, Irina
AU - Oshchepkov, Dmitry
AU - Ponomarenko, Petr
AU - Savinkova, Ludmila
AU - Oshchepkova, Evgeniya
AU - Nazarenko, Maria
AU - Kolchanov, Nikolay
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/5
Y1 - 2020/2/5
N2 - (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.
AB - (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.
KW - Atherosclerosis
KW - Candidate SNP marker
KW - Gene
KW - Human
KW - Promoter
KW - Single nucleotide polymorphism (SNP)
KW - TATA-binding protein (TBP) TBP-binding site (TATA box)
KW - Verification in vitro
KW - verification in vitro
KW - MATRIX METALLOPROTEINASE-12
KW - LOW-DENSITY-LIPOPROTEIN
KW - candidate SNP marker
KW - MITOCHONDRIAL-DNA DAMAGE
KW - NITRIC-OXIDE
KW - promoter
KW - SMOOTH-MUSCLE-CELLS
KW - human
KW - atherosclerosis
KW - TRANSCRIPTION FACTOR-BINDING
KW - FUNCTIONAL POLYMORPHISM
KW - gene
KW - HIGH-FAT DIET
KW - AMYOTROPHIC-LATERAL-SCLEROSIS
KW - HUMAN HEREDITARY-DISEASES
KW - single nucleotide polymorphism (SNP)
UR - http://www.scopus.com/inward/record.url?scp=85079084035&partnerID=8YFLogxK
U2 - 10.3390/ijms21031045
DO - 10.3390/ijms21031045
M3 - Article
C2 - 32033288
AN - SCOPUS:85079084035
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 3
M1 - 1045
ER -
ID: 23428936