DOI: 10.18413/2658-6533-2020-6-3-0-6

**Polymorphism of the VEGFA gene, smoking and coronary heart disease: the significance of gene-environmental interactions for disease susceptibility**

Maria A. Solodilova
Maria V. Medvedeva
Marina A. Bykanova
Oksana V. Vasilyeva
Vladimir P. Ivanov

Background: Coronary heart disease (CHD) is a common disease with a high mortality rate in Russia, so the problem of early prognosis and prevention of this disease is particularly relevant. In connection with the multifactorial etiology of CHD, understanding the genetic factors of the disease development for medical professionals is promising for more complete formation of risk groups among the population of our country and carrying out preventive measures. The aim of the study: To investigate the role of interactions between VEGFA gene polymorphisms and smoking in coronary heart disease (CHD) risk. Materials and methods: DNA samples from 1214 unrelated individuals (555 CHD patients and 659 controls) were genotyped for SNPs rs3025039, rs2010963, rs833061, rs3025000 and rs833068 of VEGFA by the TaqMan-based assays. Results: In this study, we found that the alleles rs2010963C, rs833061T, rs3025000T, and rs833068A were associated with increased expression of the VEGFA gene in body tissues. For the first time we have identified associations of the polymorphic variants of rs2010963, rs833061, rs3025000 and rs833068 with the risk of developing coronary heart disease exclusively in smokers, regardless of gender and age (PGxE£0,01). Conclusion: In the framework of this work, SNPs rs3025000 and rs833068 were first presented by us as genetic markers of predisposition to coronary heart disease. The considered polymorphic variants of the VEGFA gene (rs2010963, rs833061, rs3025000 and rs833068) are associated with the risk of developing heart artery disease by potentiating the negative effects of the chemical components of smoke on the formation of the atherosclerotic process in the coronary arteries.

Keywords: coronary heart disease, vascular endothelial growth factor A gene (VEGFA), single nucleotide polymorphism (SNP), smoking, gene-environment interactions, SNP annotation, epigenetic modifications.

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Solodilova MA, Medvedeva MV, Bykanova MA, et al. Polymorphism of the VEGFA gene, smoking and coronary heart disease: the significance of gene-environmental interactions for disease susceptibility. Research Results in Biomedicine. 2020;6(3):350-366. Russian. DOI: 10.18413/2658-6533-2020-6-3-0-6

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Boytsov SA, Zayratiants OV, Andreev EM, et al. Сomparison of coronary heart disease mortality in men and women age 50 years and older in Russia and USA. Russian cardiological journal. 2017;6:100-107. Russian. DOI: https://doi.org/10.15829/1560-4071-2017-6-100-107
Bokeriya LA. Cardiovascular surgery. Diseases and congenital malformations of the circulatory system. Moscow: NTSSSKH im. A.N. Bakuleva. RAMN; 2012. Russian.
Matveeva SA. Timely estimation of risk factors of coronary heart disease as a basis of prevention of its complications. 2012;90(11):19-23. Russian.
Poulter N. Coronary heart disease is a multifactorial disease. 1999;12(S6):92S-95S. DOI: https://doi.org/10.1016/S0895-7061(99)00163-6
Khera AV, Kathiresan S. Genetics of coronary artery disease: discovery, biology and clinical translation. . 2017;18(6):331-344. DOI: https://doi:10.1038/nrg.2016.160
Polonikov AV, Ivanov VP, Solodilova MA. The ecological toxicogenetic concept of multifactorial diseases: from understanding the etiology to clinical application. Medical Genetics. 2008;7(11):3-20. Russian.
Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischemic heart disease: an evaluation of evidence. BMJ. 1997;315(7114):973-980. DOI: https://doi:10.1136/bmj.315.7114.973
Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews. 2004;25(4):581-611. DOI: https://doi:10.1210/er.2003-0027
Wang Y, Huang Q, Liu J, et al. Vascular endothelial growth factor A polymorphisms are associated with increased risk of coronary heart disease: a meta-analysis. Oncotarget. 2017;8(18):30539-30551. DOI: https://10.18632/oncotarget.15546
Ma WQ, Wang Y, Han XQ, et al. Association of genetic polymorphisms in vascular endothelial growth factor with susceptibility to coronary artery disease: a meta-analysis. BMC Medical Genetics. 2018;19(1):108. DOI: https://doi:10.1186/s12881-018-0628-3
Polonikov AV, Ushachev DV, Shestakov AM, et al. Polymorphism Gly460Trp of alpha-adducin gene and predisposition to essential hypertension. The role of gene-environment interactions in the development of the disease in Russian population. Kardiologiia. 2011;51(10):33-39. Russian.
Polonikov AV, Solodilova MA, Ivanov VP, et al. A protective effect of GLY272SER polymorphism of GNB3 gene in development of essential hypertension and its relations with environmental hypertension risk factors. Therapeutic Archive. 2011;83(4):55-60. Russian.
Polonikov A, Vialykh E, Vasil'eva O, et al. Genetic variation in glutathione S-transferase genes and risk of nonfatal cerebral stroke in patients suffering from essential hypertension. Journal of Molecular Neuroscience. 2012;47(3):511-513. DOI: https://doi: 10.1007/s12031-012-9764-y
Polonikov AV, Ivanov VP, Solodilova MA. CYP2E1 gene promoter polymorphism -1293G>C increases the risk of essential hypertension in men with alcohol abuse. Bulletin of Experimental Biology and Medicine. 2013;155(6):695-698. Russian.
Bushueva OY, Bulgakova IV, Ivanov VP, et al. Association of flavin monooxygenase gene E158K polymorphism with chronic heart disease risk. Bulletin of Experimental Biology and Medicine. 2015;159(6):776-778. Russian. DOI: https://doi: 10.1007/s10517-015-3073-8
Dolzhenkova EM, Baryshev AS, Ivanova NV, et al. The relationship between polymorphism -1612 5A/6A of the MMP3 gene and 2003G>A of the MMP9 gene and ischemic heart disease risk in the population of Central Russia. Kursk Scientific and Practical Bulletin "Man and His Health". 2016;3:63-66. Russian. DOI: https://doi.org/10.21626/vestnik/2016-3/10
Sirotina S, Ponomarenko I, Kharchenko A, et al. A novel polymorphism in the promoter of the CYP4A11 gene is associated with susceptibility to coronary artery disease. Disease Markers. 2018;2018:5812802. DOI: https://doi: 10.1155/2018/5812802
Ponomarenko IV. Selection of polymorphic loci for association analysis in genetic-epidemiological studies. Research Result. Medicine and Pharmacy. 2018;4(2):40-54. Russian. DOI: 10.18413/2313-8955-2018-4- 2-0-5
Solé X, Guinó E, Valls J, et al. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928-1929. DOI: https://10.1093/bioinformatics/btl268
Shin S, Hudson R, Harrison C, et al. atSNP Search: a web resource for statistically evaluating influence of human genetic variation on transcription factor binding. Bioinformatics. 2019;35(15):2657-2659. DOI: https://doi: 10.1093/bioinformatics/bty1010
Zuo C, Shin S, Keleş S. atSNP: transcription factor binding affinity testing for regulatory SNP detection. Bioinformatics. 2015;31(20):3353-3355. DOI: https:// 10.1093/bioinformatics/btv328
Chen Y, Dawes PT, Packham JC, et al. Interaction between smoking and polymorphism in the promoter region of the VEGFA gene is associated with ischemic heart disease and myocardial infarction in rheumatoid arthritis. The Journal of Rheumatology. 2011;38(5):802-809. DOI: https://doi: 10.3899/jrheum.101095
Zhai R, Liu G, Asomaning K, et al. Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk. Carcinogenesis. 2008;29(12):2330-2334. DOI: https://doi: 10.1093/carcin/bgn210
Awata T, Inoue K, Kurihara S, et al. A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes. 2002;51(5):1635-1639. DOI: https://doi: 10.2337/diabetes.51.5.1635
Wysocka J, Swigut T, Xiao H, et al. A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature. 2006;442(7098):86-90. DOI: https://doi:10.1038/nature04815
Suming H, Litt MD, Blakey CA. Epigenetic gene expression and regulation. Oxford (UK): Academic Press; 2015.
Morris SA, Rao B, Garcia BA, et al. Identification of histone H3 lysine 36 acetylation as a highly conserved histone modification. Journal of Biological Chemistry. 2007;282(10):7632-7640. DOI: https://doi:10.1074/jbc.M607909200
Rada-Iglesias A. Is H3K4me1 at enhancers correlative or causative? Nature Genetics. 2018;50(1):4-5. DOI: https://doi: 10.1038/s41588-017-0018-3
Farid M, Kanaji N, Nakanishi M, et al. Smad3 mediates cigarette smoke extract (CSE) induction of VEGF release by human fetal lung fibroblasts. Toxicology Letters. 2013;220(2):126-134. DOI: https://doi: 10.1016/j.toxlet.2013.04.011
Oviedo A, Lebrun S, Kogel U, et al. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke. Regulatory Toxicology and Pharmacology. 2016;81(2):S93-S122. DOI: https://doi: 10.1016/j.yrtph.2016.11.004
Phillips B, Veljkovic E, Boué S, et al. An 8-month systems toxicology inhalation/cessation study in Apoe-/- mice to investigate cardiovascular and respiratory exposure effects of a candidate modified risk tobacco product, THS 2.2, compared with conventional cigarettes. Toxicological Sciences. 2016;149(2):411-432. DOI: https://doi: 10.1093/toxsci/kfv243
Iskandar AR, Martin F, Leroy P, et al. Comparative biological impacts of an aerosol from carbon-heated tobacco and smoke from cigarettes on human respiratory epithelial cultures: A systems toxicology assessment. Food and Chemical Toxicology. 2018;115:109-126. DOI: https://doi: 10.1016/j.fct.2018.02.063
Iskandar AR, Mathis C, Schlage WK, et al. A systems toxicology approach for comparative assessment: Biological impact of an aerosol from a candidate modified-risk tobacco product and cigarette smoke on human organotypic bronchial epithelial cultures. Toxicology in Vitro. 2017;39:29-51. DOI: https://doi: 10.1016/j.tiv.2016.11.009
Zanetti F, Sewer A, Mathis C, et al. Systems Toxicology Assessment of the Biological Impact of a Candidate Modified Risk Tobacco Product on Human Organotypic Oral Epithelial Cultures. Chemical Research in Toxicology. 2016;29(8):1252-1269. DOI: https://doi: 10.1021/acs.chemrestox.6b00174
Sundar IK, Nevid MZ, Friedman AE, et al. Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer. Journal of Proteome Research. 2014;13(2):982-996. DOI: https://doi: 10.1021/pr400998n
Di YP, Zhao J, Harper R. Cigarette smoke induces MUC5AC protein expression through the activation of Sp1. Journal of Biological Chemistry. 2012;287(33):27948-27958. DOI: https://doi: 10.1074/jbc.M111.334375
Yordy JS, Moussa O, Pei H, et al. SP100 inhibits ETS1 activity in primary endothelial cells. Oncogene. 2005;24(5):916-931. DOI: https://10.1038/sj.onc.1208245
ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science. 2004;306(5696):636-640. DOI: https://10.1126/science.1105136
Ng YS, Krilleke D, Shima DT. VEGF function in vascular pathogenesis. Experimental Cell Research. 2006;312(5):527-537. DOI: https://10.1016/j.yexcr.2005.11.008
Liao XH, Xiang Y, Li H, et al. VEGF-A stimulates STAT3 activity via nitrosylation of myocardin to regulate the expression of vascular smooth muscle cell differentiation markers. Scientific Reports. 2017;7(1):2660. DOI: https://doi: 10.1038/s41598-017-02907-6
Zhao Q, Egashira K, Hiasa K, et al. Essential role of vascular endothelial growth factor and Flt-1 signals in neointimal formation after periadventitial injury. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24(12):2284-2289. DOI: https://10.1161/01.ATV.0000147161.42956.80
Ohtani K, Egashira K, Hiasa K, et al. Blockade of vascular endothelial growth factor suppresses experimental restenosis after intraluminal injury by inhibiting recruitment of monocyte lineage cells. Circulation. 2004;110(16):2444-2452. DOI: https://10.1161/01.CIR.0000145123.85083.66
Lucerna M, Zernecke A, de Nooijer R, et al. Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment. Blood. 2007;109(1):122-129. DOI: https://10.1182/blood-2006-07-031773

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