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

(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.

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Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

BioMed Research International ◽

10.1155/2016/8642703 ◽

2016 ◽

Vol 2016 ◽

pp. 1-21 ◽

Cited By ~ 9

Author(s):

Petr Ponomarenko ◽

Dmitry Rasskazov ◽

Valentin Suslov ◽

Ekaterina Sharypova ◽

Ludmila Savinkova ◽

...

Keyword(s):

Q Fever ◽

Human Gene ◽

Binding Protein ◽

Early Morning ◽

Tata Binding Protein ◽

Snp Markers ◽

Hereditary Diseases ◽

Proximal Promoter ◽

Gene Promoters ◽

Nucleotide Polymorphisms

Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

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Candidate SNP markers of social dominance, which may affect the affinity of the TATA-binding protein for human gene promoters

10.18699/bgrssb-2018-012 ◽

2018 ◽

pp. 35-35

Keyword(s):

Social Dominance ◽

Human Gene ◽

Binding Protein ◽

Tata Binding Protein ◽

Snp Markers ◽

Gene Promoters

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

Russian Journal of Genetics ◽

10.1134/s1022795419090114 ◽

2019 ◽

Vol 55 (9) ◽

pp. 1137-1151 ◽

Cited By ~ 3

Author(s):

M. P. Ponomarenko ◽

D. A. Rasskazov ◽

I. V. Chadaeva ◽

E. B. Sharypova ◽

I. A. Drachkova ◽

...

Keyword(s):

Human Gene ◽

Binding Protein ◽

Tata Binding Protein ◽

Snp Markers ◽

Gene Promoters

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Candidate SNP Markers of Gender-Biased Autoimmune Complications of Monogenic Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Frontiers in Immunology ◽

10.3389/fimmu.2016.00130 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 11

Author(s):

Mikhail P. Ponomarenko ◽

Olga Arkova ◽

Dmitry Rasskazov ◽

Petr Ponomarenko ◽

Ludmila Savinkova ◽

...

Keyword(s):

Human Gene ◽

Binding Protein ◽

Tata Binding Protein ◽

Snp Markers ◽

Gene Promoters ◽

Monogenic Diseases ◽

Significant Change

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Candidate SNP markers of aggressiveness-related complications and comorbidities of genetic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters

BMC Genomics ◽

10.1186/s12864-016-3353-3 ◽

2016 ◽

Vol 17 (S14) ◽

Cited By ~ 11

Author(s):

Irina V. Chadaeva ◽

Mikhail P. Ponomarenko ◽

Dmitry A. Rasskazov ◽

Ekaterina B. Sharypova ◽

Elena V. Kashina ◽

...

Keyword(s):

Human Gene ◽

Binding Protein ◽

Genetic Diseases ◽

Tata Binding Protein ◽

Snp Markers ◽

Gene Promoters ◽

Significant Change

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Candidate SNP markers of social dominance, which may affect the affinity of the TATA-binding protein for human gene promoters

Russian Journal of Genetics Applied Research ◽

10.1134/s2079059717050045 ◽

2017 ◽

Vol 7 (5) ◽

pp. 523-537 ◽

Cited By ~ 3

Author(s):

I. V. Chadaeva ◽

D. A. Rasskazov ◽

E. B. Sharypova ◽

L. K. Savinkova ◽

P. M. Ponomarenko ◽

...

Keyword(s):

Social Dominance ◽

Human Gene ◽

Binding Protein ◽

Tata Binding Protein ◽

Snp Markers ◽

Gene Promoters

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Candidate SNP markers of rheumatoid arthritis changing the affinity of TATA-binding protein for the human gene promoters expo disruptive selection of immunoactivative and immunosuppressive genenets that provoke and prevent this disorder, respectively, as if it could be a self-domestication syndrome

Bioinformatics of Genome Regulation and Structure/ Systems Biology ◽

10.18699/bgrs/sb-2020-151 ◽

2020 ◽

Keyword(s):

Rheumatoid Arthritis ◽

Human Gene ◽

Binding Protein ◽

Tata Binding Protein ◽

Snp Markers ◽

Disruptive Selection ◽

Gene Promoters ◽

Domestication Syndrome ◽

Selection Of ◽

As If

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Сandidate SNP-markers of rheumatoid arthritis that can significantly alter the affinity of the TATA-binding protein for human gene promoters

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj19.586 ◽

2020 ◽

Vol 23 (8) ◽

pp. 1047-1058

Author(s):

I. V. Chadaeva ◽

D. A. Rasskazov ◽

E. B. Sharypova ◽

I. A. Drachkova ◽

E. A. Oshchepkova ◽

...

Keyword(s):

Human Gene ◽

Bone Erosion ◽

Binding Protein ◽

Main Idea ◽

Suppressor Cells ◽

Tata Binding Protein ◽

Snp Markers ◽

Gene Promoters ◽

T Effector Cells ◽

Myeloid Suppressor Cells

Rheumatoid polyarthritis (RA) is an autoimmune disease with autoantibodies, including antibodies to citrullant antigens and proinflammatory cytokines, such as TNF-α and IL-6, which are involved in the induction of chronic synovitis, bone erosion, followed by deformity. Immunopathogenesis is based on the mechanisms of the breakdown of immune tolerance to its own antigens, which is characterized by an increase in the activity of T-effector cells, causing RA symptomatology. At the same time, against the background of such increased activity of effector lymphocytes, a decrease in the activity of a number of regulatory cells, including regulatory T-cells (Treg) and myeloid suppressor cells, is recorded. There is reason to say that it is the change in the activity of suppressor cells that is the leading element in RA pathogenesis. That is why only periods of weakening (remission) of RA are spoken of. According to the more powerful female immune system compared to the male one, the risk of developing RA in women is thrice as high, this risk decreases during breastfeeding and grows during pregnancy as well as after menopause in proportion to the level of sex hormones. It is believed that 50 % of the risk of developing RA depends on the conditions and lifestyle, while the remaining 50 % is dependent on genetic predisposition. That is why, RA fits the main idea of postgenomic predictive-preventive personalized medicine that is to give a chance to those who would like to reduce his/her risk of diseases by bringing his/her conditions and lifestyle in line with the data on his/her genome sequenced. This is very important, since doctors consider RA as one of the most frequent causes of disability. Using the Web service SNP_TATA_Z-tester (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl), 227 variants of single nucleotide polymorphism (SNP) of the human gene promoters were studied. As a result, 43 candidate SNP markers for RA that can alter the affinity of the TATA-binding protein (TBP) for the promoters of these genes were predicted.

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