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

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Abstract

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, http://www.ssg.uab.edu/gmdr). 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

Email: mariam31011989@yandex.ru
Ph.D., senior lecturer of the department medical and biological sciences Belgorod

Alexey V. Polonikov

Kursk State Medical University

Email: polonikov@rambler.ru
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

Email: sorokina@bsu.edu.ru
Doctor of Biological Sciences, Professor, Department of Biomedical Disciplines Belgorod

Tatyana I. Yakunchenko

Belgorod National Research University

Email: yakunchenko@bsu.edu.ru
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

Email: krikun@bsu.edu.ru
Doctor of Medical Sciences, director of medical college Belgorod

Irina V. Ponomarenko

Belgorod National Research University

Email: ponomarenko_i@bsu.edu.ru
Ph.D., senior lecturer of the department medical and biological sciences of the medical institute Belgorod

Evgeniy Aleksandrovich Klimov

Email: klimov_eugeney@mail.ru

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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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