Gene-environment interactions between polymorphic loci of MMPs and obesity in essential hypertension in women.

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BACKGROUND. The prevalence of essential hypertension (ЕH) is increasing every year, both in Russia and around the world. Genetic and environmental risk factors are involved in the development of hypertension, and obesity plays an important role. Therefore, the study of gene-ecological interactions in the development of hypertension seems to be relevant. AIMS: to study the gene-environment interactions between polymorphic loci of MMP and obesity in essential hypertension in women. MATERIALS AND METHODS. The study was conducted in a case-control design. The sample included 584 subjects: 375 patients with EH and 209 women in the control group. All individuals included in the study were genotyped for eight polymorphic loci of MMPs. The study of the gene-environmental interactions during the formation of hypertension was performed using the GMDR method (Generalized Multifactor Dimensionality Reduction, RESULTS. rs11568818 MMР7 and rs11225395 MMР8 polymorphic loci were found to be involved in the development of arterial hypertension in women without obesity (p<0.050). Fifteen three-, four-, and five-factor models of gene-environmental interactions of 8 MMPs with obesity, associated with EH (p=0.01), were found. It is shown that the analyzed SNPs are located in the DNA regions that bind to histones, marking promoters and enhancers, in the region of hypersensitivity to DNAse-1, in the binding sites of regulatory proteins and transcription factors. The loci of MMPs rs17577, rs11568818, rs1320632 and rs11225395 have cis-eQTL-value. They affecting the expression of the genes of MMP7, SNX21, SLC12A5 and RP11-817J15.3. CONCLUSIONS. SNP rs11568818 MMP7 and rs11225395 MMP8 and gene-environmental interactions of MMPs rs1799750, rs243865, rs3025058, rs11568818, rs1320632, rs11225395, rs17577, rs652438 with obesity are involved in the development of essential hypertension in women.

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About the authors

Maria I. Moskalenko

Belgorod National Research University

Ph.D., senior lecturer of the department medical and biological sciences Belgorod

Alexey V. Polonikov

Kursk State Medical University

Doctor of Medical Sciences, Professor, Professor of the Department of Biology, Medical Genetics and Ecology, director of the Research Institute of Genetic and Molecular Epidemiology Kursk

Inna N. Sorokina

Belgorod National Research University

Doctor of Biological Sciences, Professor, Department of Biomedical Disciplines Belgorod

Tatyana I. Yakunchenko

Belgorod National Research University

Doctor of Medical Sciences, Head of the Department of Propedeutics of Internal Diseases and Clinical Information Technologies Белгород

Yevgeniy N. Krikun

Belgorod National Research University

Doctor of Medical Sciences, director of medical college Belgorod

Irina V. Ponomarenko

Belgorod National Research University

Ph.D., senior lecturer of the department medical and biological sciences of the medical institute Belgorod

Evgeniy Aleksandrovich Klimov



  1. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet (London, England). 2017;389(10064):37-55. doi:
  2. Бритов А.Н., Поздняков Ю.М., Волкова Э.Г., и др. Национальные рекомендации по кардиоваскулярной профилактике. Кардиоваскулярная терапия и профилактика. 2011;10:6:2-64. Britov AN, Pozdnyakov YM, Volkova EG, et al. Natsional’nyye rekomendatsii po kardiovaskulyarnoy profilaktike. Cardiovascular therapy and prevention. 2011;10(6):2-64. (In Russ.).
  3. Nguyen DM, El-Serag HB. The epidemiology of obesity. Gastroenterol Clin North Am. 2010;39:1-7. doi:
  4. Болотов И.И. Влияние пептида KED на экспрессию коннексина и сиртуина при атеросклерозе и рестенозе у людей пожилого возраста. Научные результаты биомедицинских исследований. 2018;4:4:60-68. Bolotov II. Effects of KED peptide on connexin and sirutin expression in atherosclerosis and restinosis in elderly people. Research results in biomedicine. 2018;4(4):60-68. (In Russ.). doi:
  5. Kidambi S, Kotchen TA. Treatment of hypertension in obese patients. Am J Cardiovasc Drugs. 2013;13:163-175. doi:
  6. Young DA, Barter MJ, Wilkinson DJ. Recent advances in understanding the regulation of metalloproteinases. F1000Res. 2019;8: 1000-1195. doi:
  7. Антонов И.Б. Экспрессия белков MMP при старении миокарда в норме и при дилатационной кардиомиопатии. Научные результаты биомедицинских исследований. 2019;5:1:122-130. Antonov IB. Expression of MMP proteins in the aging of the myocardium in normal conditions and dilated cardiomyopathy. Research results in biomedicine. 2019;5(1):122-130. (In Russ.). doi:
  8. Polonikov A, Rymarova L, Klyosova E, et al. Matrix metalloproteinases as target genes for gene regulatory networks driving molecular and cellular pathways related to a multistep pathogenesis of cerebrovascular disease. J Cell Biochem. 2019;120(10):16467-16482. doi:
  9. Boumiza S, Bchir S, Ben Nasr H, et al. Role of MMP-1 (-519A/G, -1607 1G/2G), MMP-3 (Lys45Glu), MMP-7 (-181A/G), and MMP-12 (-82A/G) variants and plasma MMP levels on obesity-related phenotypes and microvascular reactivity in a tunisian population. Dis Markers. 2017;6198526. doi:
  10. Москаленко М.И., Пономаренко И.В., Полоников А.В., Чурносов М.И. Полиморфный локус RS11568818 гена MMР7 ассоциирован с развитием артериальной гипертонии у женщин. Российский кардиологический журнал. 2018;23:10:14-17. Moskalenko MI, Ponomarenko IV, Polonikov AV, Churnosov MI. Polymorphic locus RS11568818 of the MMP7 gene is associated with the development of essеntial hypertension in women. Russian journal of cardiology. 2018;23(10):14-17. (In Russ.). doi:
  11. Beilby JP, Chapman CM, Palmer LJ. Stromelysin-1 (MMP-3) gene 5A/6A promoter polymorphism is associated with blood pressure in a community population. J Hypertens. 2005;23(3):537-542. doi:
  12. Москаленко М.И., Пономаренко И.В., Полоников А.В., Чурносов М.И. Полиморфный локус rs652438 гена MMP12 ассоциирован с развитием артериальной гипертензии у женщин. Артериальная гипертензия. 2019;25:1:60-65. Moskalenko MI, Ponomarenko IV, Polonikov AV, Churnosov MI. Polymorphic locus rs652438 of the MMP12 gene is associated with the development of hypertension in women. Arterial hypertension. 2019;25(1):60-65. (In Russ.). doi:
  13. Polonikov AV, Bushueva OY, Bulgakova IV, et al. A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility. Pharmacogenet Genomics. 2017;(2):57-69. doi:
  14. Hettiaratchi A, Hawkins NJ, McKenzie G, et al. The collagenase-1 (MMP-1) gene promoter polymorphism -1607/2G is associated with favourable prognosis in patients with colorectal cancer. Br J Cancer. 2007;96(5):783-792. doi:
  15. Lièvre A, Milet J, Carayol J, et al. Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma. BMC Cancer. 2006;6:270. doi:
  16. Pradhan-Palikhe P, Pussinen PJ, Vikatmaa P, et al. Single nucleotide polymorphism -799C/T in matrix metalloproteinase-8 promoter region in arterial disease. Innate Immun. 2012;18(3):511-517. doi:
  17. Ward LD, Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 2016;44:877-881. doi:
  18. Battle A, Brown CD, Engelhardt BE, Montgomery SB; GTEx Consortium, et al. Genetic effects on gene expression across human tissues. Nature. 2017;550(7675):204-213. doi:
  19. Chavey C, Mari B, Monthouel MN, et al. Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J Biol Chem. 2003;278:11888-11896. doi:
  20. Andrade VL, Petruceli E, Belo VA, et al. Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women. Clin Biochem. 2012;45(6):412-415. doi:
  21. Glowinska-Olszewska B, Urban M. Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents. Metabolism. 2007;56(6):799-805. doi:
  22. Hoseini SM, Kalantari A, Afarideh M, et al. Evaluation of plasma MMP-8, MMP-9 and TIMP-1 identifies candidate cardiometabolic risk marker in metabolic syndrome: results from double-blinded nested case-control study. Metabolism. 2015;64(4):527-538. doi:
  23. Jormsjö S, Whаtling C, Wаlter DH, et al. Аllele-specific regulаtion of mаtrix metаlloproteinаse-7 promoter аctivity is аssociаted with coronаry аrtery luminаl dimensions аmong hypercholesterolemic pаtients. Аrterioscler Thrombos Vаsc Biol. 2001;21:1834-1839. doi:

Copyright (c) 2019 Moskalenko M.I., Polonikov A.V., Sorokina I.N., Yakunchenko T.I., Krikun Y.N., Ponomarenko I.V., Klimov E.A.

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