<?xml version='1.0' encoding='utf-8'?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2020-6-4-0-1</article-id><article-id pub-id-type="publisher-id">2176</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;Single nucleotide polymorphisms in genes encoding xenobiotic metabolizing enzymes are associated with predisposition to arterial hypertension&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;Single nucleotide polymorphisms in genes encoding xenobiotic metabolizing enzymes are associated with predisposition to arterial hypertension&lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Bushueva</surname><given-names>Olga Yu.</given-names></name><name xml:lang="en"><surname>Bushueva</surname><given-names>Olga Yu.</given-names></name></name-alternatives><email>olga.bushueva@inbox.ru</email></contrib></contrib-group><pub-date pub-type="epub"><year>2020</year></pub-date><volume>6</volume><issue>4</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2020/4/Биомед._Выпуск_4_2020-6-15.pdf" /><abstract xml:lang="ru"><p>Background: Arterial hypertension (AH) is the most common disease of the cardiovascular system. Intracellular chemical and oxidative stress, which can be associated both with direct exposure to toxic xenobiotics and with their excessive activation during biotransformation, may lead to endothelial dysfunction and increased risk of AH development. The aim of the study: To investigate the association of single nucleotide polymorphisms of genes involved in the biotransformation of xenobiotics (rs1048943 CYP1A1, rs762551 CYP1A2, rs1056836 CYP1B1, rs1799930 NAT2, rs1800566 NQO1, rs11045642 MDR1) with predisposition to arterial hypertension. Materials and methods: A total of 702 patients with AH (307 men, 395 women; mean age 55 years) and 857 gender- and age- matched relatively healthy volunteers (406 men, 451 women; mean age 53 years) were recruited for the study. Genotyping of SNPs were done using TaqMan-based PCR. Results: Comparative analysis of genotype frequencies (log-additive regression model was used, all calculations were performed with adjustment for gender, age) showed that SNP rs762551 CYP1A2 was associated with a decreased risk of AH (ORadj=0.85, 95%CIadj=0.73-0.99; Padj=0.038); SNP rs1045642 MDR1 (ABCB1) was associated with an increased risk of AH (ORadj=1.20, 95% CIadj=1.04-1.39; Padj=0.013). Moreover, SNP rs762551 CYP1A2 was associated with the age of manifestation of arterial hypertension (Differenceadj=1.51; 95%CIadj=0.22-2.80) and cholesterol level (Differenceadj= -0.15; 95% Cladj = -0.29 - -0.01). Conclusion: Thus, in this study, for the first time, there was found the association of rs762551 CYP1A2 and rs1045642 ABCB1 (MDR1) with arterial hypertension in Russians.</p></abstract><trans-abstract xml:lang="en"><p>Background: Arterial hypertension (AH) is the most common disease of the cardiovascular system. Intracellular chemical and oxidative stress, which can be associated both with direct exposure to toxic xenobiotics and with their excessive activation during biotransformation, may lead to endothelial dysfunction and increased risk of AH development. The aim of the study: To investigate the association of single nucleotide polymorphisms of genes involved in the biotransformation of xenobiotics (rs1048943 CYP1A1, rs762551 CYP1A2, rs1056836 CYP1B1, rs1799930 NAT2, rs1800566 NQO1, rs11045642 MDR1) with predisposition to arterial hypertension. Materials and methods: A total of 702 patients with AH (307 men, 395 women; mean age 55 years) and 857 gender- and age- matched relatively healthy volunteers (406 men, 451 women; mean age 53 years) were recruited for the study. Genotyping of SNPs were done using TaqMan-based PCR. Results: Comparative analysis of genotype frequencies (log-additive regression model was used, all calculations were performed with adjustment for gender, age) showed that SNP rs762551 CYP1A2 was associated with a decreased risk of AH (ORadj=0.85, 95%CIadj=0.73-0.99; Padj=0.038); SNP rs1045642 MDR1 (ABCB1) was associated with an increased risk of AH (ORadj=1.20, 95% CIadj=1.04-1.39; Padj=0.013). Moreover, SNP rs762551 CYP1A2 was associated with the age of manifestation of arterial hypertension (Differenceadj=1.51; 95%CIadj=0.22-2.80) and cholesterol level (Differenceadj= -0.15; 95% Cladj = -0.29 - -0.01). Conclusion: Thus, in this study, for the first time, there was found the association of rs762551 CYP1A2 and rs1045642 ABCB1 (MDR1) with arterial hypertension in Russians.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>arterial hypertension</kwd><kwd>cytochrome P450</kwd><kwd>biotransformation of xenobiotics</kwd><kwd>rs762551</kwd><kwd>CYP1A2</kwd><kwd>rs1045642</kwd><kwd>MDR1</kwd><kwd>ABCB1</kwd></kwd-group><kwd-group xml:lang="en"><kwd>arterial hypertension</kwd><kwd>cytochrome P450</kwd><kwd>biotransformation of xenobiotics</kwd><kwd>rs762551</kwd><kwd>CYP1A2</kwd><kwd>rs1045642</kwd><kwd>MDR1</kwd><kwd>ABCB1</kwd></kwd-group></article-meta></front><back><ack><p>I would like to expresses my gratitude to my colleagues, Professor V.P. Ivanov, as well as Professor A.V. Polonikov for valuable suggestions in carrying out this research.</p></ack><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Mills KT, Bundy JD, Kelly TN, et al. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries.&amp;nbsp;Circulation. 2016;134(6):441-450. DOI: https://doi.org/10.1161/CIRCULATIONAHA.115.018912</mixed-citation></ref><ref id="B2"><mixed-citation>Holme JA, Brinchmann BC, Refsnes M, et al. Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles.&amp;nbsp;Environmental Health. 2019;18(1):74. DOI: https://doi.org/10.1186/s12940-019-0514-2</mixed-citation></ref><ref id="B3"><mixed-citation>Manisalidis I, Stavropoulou E, Stavropoulos A, et al. Environmental and Health Impacts of Air Pollution: A Review. Frontiers in Public Health. 2020;8:14. DOI: https://doi.org/10.3389/fpubh.2020.00014</mixed-citation></ref><ref id="B4"><mixed-citation>Wu H, Lu L, Chen J, et al. Inhibited Nitric Oxide Production of Human Endothelial Nitric Oxide Synthase by Nitrated and Oxygenated Polycyclic Aromatic Hydrocarbons. Environmental Science &amp;amp; Technology. 2020;54(5):2922-2930. DOI: https://doi.org/10.1021/acs.est.9b07163</mixed-citation></ref><ref id="B5"><mixed-citation>Gheibi S, Jeddi S, Kashfi K, et al. Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension. Biochemical Pharmacology. 2018;149:42-59. DOI: https://doi.org/10.1016/j.bcp.2018.01.017</mixed-citation></ref><ref id="B6"><mixed-citation>Mescher M, Haarmann-Stemmann T. Modulation of CYP1A1 metabolism: From adverse health effects to chemoprevention and therapeutic options. Pharmacology and Therapeutics. 2018;187:71-87. DOI: https://doi.org/10.1016/j.pharmthera.2018.02.012</mixed-citation></ref><ref id="B7"><mixed-citation>Hankinson O. The role of AHR-inducible cytochrome P450s in metabolism of polyunsaturated fatty acids. Drug Metabolism Reviews. 2016;48(3):342-350. DOI: https://doi.org/10.1080/03602532.2016.1197240</mixed-citation></ref><ref id="B8"><mixed-citation>Tarnow P, Tralau T, Luch A. Chemical activation of estrogen and aryl hydrocarbon receptor signaling pathways and their interaction in toxicology and metabolism. Expert Opinion on Drug Metabolism and Toxicology. 2019;15(3):219-229. DOI: https://doi.org/10.1080/17425255.2019.1569627</mixed-citation></ref><ref id="B9"><mixed-citation>Gastelum G, Jiang W, Wang L, et al. Polycyclic Aromatic Hydrocarbon (PAH)-Induced Pulmonary Carcinogenesis in Cytochrome P450 (CYP) 1A1- and 1A2-null Mice: Roles of CYP1A1 and CYP1A2. Toxicological Sciences. 2020;177(2):347-361. DOI: https://doi.org/10.1093/toxsci/kfaa107</mixed-citation></ref><ref id="B10"><mixed-citation>Chen Y, Zeng L, Wang Y, et al. The expression, induction and pharmacological activity of CYP1A2 are post-transcriptionally regulated by microRNA hsa-miR-132-5p.&amp;nbsp;Biochemical Pharmacology. 2017;145:178-191. DOI: https://doi.org/10.1016/j.bcp.2017.08.012</mixed-citation></ref><ref id="B11"><mixed-citation>Ibrahim M, MacFarlane EM, Matteo G, et al. Functional cytochrome P450 1A enzymes are induced in mouse and human islets following pollutant exposure.&amp;nbsp;Diabetologia. 2020;63(1):162-178. DOI: https://doi.org/10.1007/s00125-019-05035-0</mixed-citation></ref><ref id="B12"><mixed-citation>Koonrungsesomboon N, Khatsri R, Wongchompoo P, et al. The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. Pharmacogenomics Journal. 2018;18(6):760-768. DOI: https://doi.org/10.1038/s41397-017-0011-3</mixed-citation></ref><ref id="B13"><mixed-citation>Falero-Perez J, Song YS, Sorenson CM, Sheibani N. CYP1B1: A key regulator of redox homeostasis.&amp;nbsp;Trends in Cell Biology. 2018;13:27-45.</mixed-citation></ref><ref id="B14"><mixed-citation>Jennings BL, Sahan-Firat S, Estes AM, et al. Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology. Hypertension. 2010;56(4):667-674. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.110.154518</mixed-citation></ref><ref id="B15"><mixed-citation>Docea AO, Vassilopoulou L, Fragou D, et al. CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides. Toxicology Reports. 2017;4:335-341. DOI: https://doi.org/10.1016/j.toxrep.2017.05.007</mixed-citation></ref><ref id="B16"><mixed-citation>Conway LP, Rendo V, Correia MSP, et al. Unexpected Acetylation of Endogenous Aliphatic Amines by Arylamine N-Acetyltransferase NAT2. Angewandte Chemie - International Edition. 2020;59(34):14342-14346. DOI: https://doi.org/10.1002/anie.202005915</mixed-citation></ref><ref id="B17"><mixed-citation>Mitchell SC. N-acetyltransferase: the practical consequences of polymorphic activity in man. Xenobiotica. 2020;50(1):77-91. DOI: https://doi.org/10.1080/00498254.2019.1618511</mixed-citation></ref><ref id="B18"><mixed-citation>Ross D, Siegel D. NQO1 in protection against oxidative stress. . 2018;7:67-72. DOI: https://doi.org/10.1016/j.cotox.2017.10.005</mixed-citation></ref><ref id="B19"><mixed-citation>Gu&amp;eacute;niche N, Bruyere A, Le V&amp;eacute;e M, et al. Implication of human drug transporters to toxicokinetics and toxicity of pesticides. Pest Management Science. 2020;76(1):18-25. DOI: https://doi.org/10.1002/ps.5577</mixed-citation></ref><ref id="B20"><mixed-citation>Wang L, Yang L, Zhang J, et al. Association of ABCB1 C3435T Polymorphism with Echocardiographic Index Among Patients with Atherosclerotic Ischemic Stroke and Transient Ischemic Attack. Journal of Molecular Neuroscience. 2020;70(9):1445-1450. DOI: https://doi.org/10.1007/s12031-020-01567-y</mixed-citation></ref><ref id="B21"><mixed-citation>Bushueva OY, Ivanov VP, Ryzhaeva VN, et al. Association of the -844G&amp;gt;A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers. Terapevticheskii Arkhiv. 2016;88(9):50-54. Russian. DOI: https://doi.org/10.17116/terarkh201688950-54</mixed-citation></ref><ref id="B22"><mixed-citation>Polonikov AV, Bushueva OY, Bulgakova IV, et al. A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility. Pharmacogenetics and Genomics. 2017;27(2):57-69. DOI: https://doi.org/10.1097/FPC.0000000000000261</mixed-citation></ref><ref id="B23"><mixed-citation>Polonikov A, Bykanova M, Ponomarenko I, et al. The contribution of CYP2C gene subfamily involved in epoxygenase pathway of arachidonic acids metabolism to hypertension susceptibility in Russian population. Clinical and Experimental Hypertension. 2017;39(4):306-311. DOI: https://doi.org/10.1080/10641963.2016.1246562</mixed-citation></ref><ref id="B24"><mixed-citation>Palatini P, Ceolotto G, Ragazzo F, et al. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. Journal of Hypertension. 2009;27(8):1594-1601. DOI: https://doi.org/10.1097/HJH.0b013e32832ba850</mixed-citation></ref><ref id="B25"><mixed-citation>Newton-Cheh C, Johnson T, Gateva V, et al. Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics. 2009;41(6):666-676. DOI: https://doi.org/10.1038/ng.361</mixed-citation></ref><ref id="B26"><mixed-citation>Guessous I, Dobrinas M, Kutalik Z, et al. Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension. Human Molecular Genetics. 2012;21(14):3283-3292. DOI: https://doi.org/10.1093/hmg/dds137</mixed-citation></ref><ref id="B27"><mixed-citation>Veith A, Moorthy B. Role of cytochrome P450s in the generation and metabolism of reactive oxygen species. . 2018;7:44-51. DOI: https://doi.org/10.1016/j.cotox.2017.10.003</mixed-citation></ref><ref id="B28"><mixed-citation>Smith AG, Davies R, Dalton TP, et al. Intrinsic hepatic phenotype associated with the Cyp1a2 gene as shown by cDNA expression microarray analysis of the knockout mouse. EHP toxicogenomics : journal of the National Institute of Environmental Health Sciences. 2003;111(1T):45-51.</mixed-citation></ref><ref id="B29"><mixed-citation>Frye RF, Schneider VM, Frye CS, et al. Plasma levels of TNF-alpha and IL-6 are inversely related to cytochrome P450-dependent drug metabolism in patients with congestive heart failure. Journal of Cardiac Failure. 2002;8(5):315-319. DOI: https://doi.org/10.1054/jcaf.2002.127773</mixed-citation></ref><ref id="B30"><mixed-citation>Efferth T, Volm M. Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers. Archives of Toxicology. 2017;91(7):2515-2538. DOI: https://doi.org/10.1007/s00204-017-1938-5</mixed-citation></ref><ref id="B31"><mixed-citation>Wang D, Johnson AD, Papp AC, et al. Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C&amp;gt;T affects mRNA stability. Pharmacogenetics and Genomics. 2005;15(10):693-704. DOI: https://doi.org/10.1097/01.fpc.0000178311.02878.83</mixed-citation></ref><ref id="B32"><mixed-citation>Zhang XW, Yang JL, Liang W, et al. Genetic association study of ABCB1 gene polymorphisms with hypertension in Han Chinese population. European Review for Medical and Pharmacological Sciences. 2016;20(17):3661-3671.</mixed-citation></ref><ref id="B33"><mixed-citation>Liu M, Li Y, Citterio L, et al. A functional common polymorphism of the ABCB1 gene is associated with chronic kidney disease and hypertension in Chinese. American Journal of Hypertension. 2013;26(12):1428-1436. DOI: https://doi.org/10.1093/ajh/hpt126</mixed-citation></ref><ref id="B34"><mixed-citation>Bello-Reuss E, Ernest S, Holland OB, et al. Role of multidrug resistance P-glycoprotein in the secretion of aldosterone by human adrenal NCI-H295 cells. American Journal of Physiology - Cell Physiology. 2000;278(6):C1256-C1265. DOI: https://doi.org/10.1152/ajpcell.2000.278.6.C1256</mixed-citation></ref><ref id="B35"><mixed-citation>Sita G, Hrelia P, Tarozzi A, et al. P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer&amp;#39;s Disease. Oxidative Medicine and Cellular Longevity. 2017;2017:7905486. DOI: https://doi.org/10.1155/2017/7905486</mixed-citation></ref><ref id="B36"><mixed-citation>Widder JD, Guzik TJ, Mueller CF, et al. Role of the multidrug resistance protein-1 in hypertension and vascular dysfunction caused by angiotensin II. Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27(4):762-768. DOI: https://doi.org/10.1161/01.ATV.0000259298.11129.a2</mixed-citation></ref><ref id="B37"><mixed-citation>Kim J.H., Hong Y.C. The effect of exposure to air pollutants on insulin resistance modified by genotypes of GSTM1 and NAT2 in the Korean elderly environmental panel study (KEEPS). ISEE Conference Abstracts. 2011;1. DOI: https://doi.org/10.1289/isee.2011.00985</mixed-citation></ref><ref id="B38"><mixed-citation>Paul S, Ahmed S, Khan I, et al. Type 2 diabetes mellitus (T2DM) subjects of Bangladeshi origin with fast N-acetyltransferase 2 (NAT2) acetylator phenotype show lower insulin sensitivity than slow acetylator phenotype. International Journal of Diabetes in Developing Countries. 2013;33:213-218. 10.1007/s13410-013-0144-0</mixed-citation></ref></ref-list></back></article>