medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.1234/XXXX-XXXX-2015-10-29-35medgen-59Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПолиморфизм генов системы эндотелина-1 и риск эссенциальной гипертензииPolymorphisms of endothelin-1 system genes and risk of essential hypertensionТимашеваЯ. Р.TimashevaY. R.ianina_t@mail.ruНасибуллинТ. Р.NasibullinT. R.noemail@neicon.ruИмаеваЭ. Б.ImaevaE. B.noemail@neicon.ruМирсаеваГ. Х.MirsaevaG. Kh.noemail@neicon.ruМустафинаО. Е.MustafinaO. E.noemail@neicon.ruИнститут биохимии и генетики Уфимского научного центра Российской академии наукРоссияInstitute if Biochemistry and Genetics of Ufa Scientific Centre of Russian Academy of SciencesRussian FederationБашкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian Federation20151606201614102935Copyright © Тимашева Я.Р., Насибуллин Т.Р., Имаева Э.Б., Мирсаева Г.Х., Мустафина О.Е., 20162016Тимашева Я.Р., Насибуллин Т.Р., Имаева Э.Б., Мирсаева Г.Х., Мустафина О.Е.Timasheva Y.R., Nasibullin T.R., Imaeva E.B., Mirsaeva G.K., Mustafina O.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/59

Система эндотелина-1 играет важную роль в регуляции сосудистого тонуса и процессе ремоделирования сосудов. Цель настоящего исследования состояла в проведении анализа ассоциаций с эссенциальной гипертензией полиморфных вариантов генов эндотелина-1, эндотелинпревращающего фермента, рецепторов эндотелина А и В в этнической группе татар, проживающих в Республике Башкортостан. Нами обнаружена ассоциация полиморфных вариантов rs6842241 гена EDNRA и rs5351 гена EDNRB с эссенциальной гипертензией у мужчин. Кроме того, повышенный риск эссенциальной гипертензии был отмечен у носителей сочетания генотипа EDNRA *G/G и аллеля EDNRB *C, а сочетание аллелей EDNRA *C и EDNRB *A обладало протективным эффектом в отношении развития заболевания.

Endothelin-1 system plays an important role in regulation of vascular tone and vascular remodeling. The aim of the current study was to perform an analysis of association between essential hypertension and polymorphic variants in genes, encoding endothelin-1, endothelin-converting enzyme, endothelin receptors A and B, in the ethnic group of Tatars residing in the Republic of Bashkortostan. We found an association of EDNRA rs6842241 and EDNRB rs5351 polymorphic variants with essential hypertension in men. Furthermore, an increased risk of essential hypertension was detected for the carriers of EDNRA *G/G genotype and EDNRB *C allele combination, while EDNRA *C and EDNRB *A alleles combination had protective effect against the development of the disease.

эссенциальная гипертензиягенетический полиморфизмрецепторы эндотелина A и BAPSampleressential hypertensiongenetic polymorphismendothelin receptors A and BAPSamplerReferencesAn S.J. et al. Endothelin-1 expression in vascular adventitial fibroblasts // American Journal of Physiology-Heart and Circulatory Physiology. - 2006. - Vol. 290, № 2. - H700-H708.An S.J. et al. Endothelin-1 expression in vascular adventitial fibroblasts // American Journal of Physiology-Heart and Circulatory Physiology. - 2006. - Vol. 290, № 2. - H700-H708.Asai T. et al. Endothelin-1 Gene Variant Associates With Blood Pressure in Obese Japanese Subjects The Ohasama Study // Hypertension. - 2001. - Vol. 38, № 6. - P. 1321-1324.Asai T. et al. Endothelin-1 Gene Variant Associates With Blood Pressure in Obese Japanese Subjects The Ohasama Study // Hypertension. - 2001. - Vol. 38, № 6. - P. 1321-1324.Banno M., Hanada H., Kamide K. et al. Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives // Hypertension Research. - 2007. - Vol. 30, № 6. - P. 513.Banno M., Hanada H., Kamide K. et al. Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives // Hypertension Research. - 2007. - Vol. 30, № 6. - P. 513.Barden A.E., Herbison C.E., Beilin L.J. et al. Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy // Journal of hypertension. - 2001. - Vol. 19, № 10. - P. 1775-1782.Barden A.E., Herbison C.E., Beilin L.J. et al. Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy // Journal of hypertension. - 2001. - Vol. 19, № 10. - P. 1775-1782.Benjafield A.V., Katyk K., Morris B.J. Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension // Clinical genetics. - 2003. - Vol. 64, № 5. - P. 433-438.Benjafield A.V., Katyk K., Morris B.J. Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension // Clinical genetics. - 2003. - Vol. 64, № 5. - P. 433-438.Caprioli J. et al. Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension // Canadian journal of physiology and pharmacology. - 2008. - Vol. 86, № 8. - P. 505-510.Caprioli J. et al. Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension // Canadian journal of physiology and pharmacology. - 2008. - Vol. 86, № 8. - P. 505-510.Chade A.R., Stewart N.J., Peavy P.R. Disparate effects of single endothelin-A and-B receptor blocker therapy on the progression of renal injury in advanced renovascular disease // Kidney international. - 2014. - Vol. 85, № 4. - P. 833-844.Chade A.R., Stewart N.J., Peavy P.R. Disparate effects of single endothelin-A and-B receptor blocker therapy on the progression of renal injury in advanced renovascular disease // Kidney international. - 2014. - Vol. 85, № 4. - P. 833-844.de Zeeuw D. et al. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy // J. Am. Soc. Nephrol. - 2014. - Vol. 25, № 5. - P. 1083-1093.de Zeeuw D. et al. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy // J. Am. Soc. Nephrol. - 2014. - Vol. 25, № 5. - P. 1083-1093.D’Orleans-Juste P. et al. Synthesis and degradation of endothelin-1 // Canadian journal of physiology and pharmacology. - 2003. - Vol. 81, № 6. - P. 503-510.D’Orleans-Juste P. et al. Synthesis and degradation of endothelin-1 // Canadian journal of physiology and pharmacology. - 2003. - Vol. 81, № 6. - P. 503-510.Dzholdasbekova A.U., Gaipov A.E. The association between polymorphism of Lys198Asn of endothelin-1 gene and arterial hypertension risk in Kazakh people // European Journal of General Medicine. - 2010. - Vol. 7, № 2.Dzholdasbekova A.U., Gaipov A.E. The association between polymorphism of Lys198Asn of endothelin-1 gene and arterial hypertension risk in Kazakh people // European Journal of General Medicine. - 2010. - Vol. 7, № 2.Favorov A.V. et al. A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans // Genetics. - 2005. - Vol. 171, № 4. - P. 2113-2121.Favorov A.V. et al. A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans // Genetics. - 2005. - Vol. 171, № 4. - P. 2113-2121.Funalot B., Courbon D., Brousseau T. et al. Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study // Journal of hypertension. - 2004. - Vol. 22, № 4. - P. 739-743.Funalot B., Courbon D., Brousseau T. et al. Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study // Journal of hypertension. - 2004. - Vol. 22, № 4. - P. 739-743.Funke-Kaiser H. et al. Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation // Human molecular genetics. - 2003. - Vol. 12, № 4. - P. 423-433.Funke-Kaiser H. et al. Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation // Human molecular genetics. - 2003. - Vol. 12, № 4. - P. 423-433.Gu D., Zhao Q., Kelly T.N. et al. The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure The GenSalt Study // American journal of epidemiology. - 2012. - Vol. 176. - Suppl 7. - P. S72-S80.Gu D., Zhao Q., Kelly T.N. et al. The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure The GenSalt Study // American journal of epidemiology. - 2012. - Vol. 176. - Suppl 7. - P. S72-S80.Hiyama T.Y. et al. Endothelin-3 expression in the subfornical organ enhances the sensitivity of Na x, the brain sodium-level sensor, to suppress salt intake // Cell metabolism. - 2013. - Vol. 17, № 4. - P. 507-519.Hiyama T.Y. et al. Endothelin-3 expression in the subfornical organ enhances the sensitivity of Na x, the brain sodium-level sensor, to suppress salt intake // Cell metabolism. - 2013. - Vol. 17, № 4. - P. 507-519.Iemitsu M. et al. Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects // Hypertension. - 2006. - Vol. 47, № 5. - P. 928-936.Iemitsu M. et al. Polymorphism in endothelin-related genes limits exercise-induced decreases in arterial stiffness in older subjects // Hypertension. - 2006. - Vol. 47, № 5. - P. 928-936.Jiang C. et al. Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1 // American Journal of Physiology-Heart and Circulatory Physiology. - 1992. - Vol. 263, № 1. - P. H271-H275.Jiang C. et al. Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1 // American Journal of Physiology-Heart and Circulatory Physiology. - 1992. - Vol. 263, № 1. - P. H271-H275.Jin J.J., Nakura J., Wu Z. et al. Association of endothelin-1 gene variant with hypertension // Hypertension. - 2003. - Vol. 41, № 1. - P. 163-167.Jin J.J., Nakura J., Wu Z. et al. Association of endothelin-1 gene variant with hypertension // Hypertension. - 2003. - Vol. 41, № 1. - P. 163-167.Kohan D.E. et al. Regulation of blood pressure and salt homeostasis by endothelin // Physiological reviews. - 2011. - Vol. 91, № 1. - P. 1-77.Kohan D.E. et al. Regulation of blood pressure and salt homeostasis by endothelin // Physiological reviews. - 2011. - Vol. 91, № 1. - P. 1-77.Lenoir O. et al. Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis // Journal of the American Society of Nephrology. - 2014. - Vol. 25, № 5. - P. 1050-1062.Lenoir O. et al. Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis // Journal of the American Society of Nephrology. - 2014. - Vol. 25, № 5. - P. 1050-1062.Ling L., Maguire J.J., Davenport A.P. Endothelin-2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer // British journal of pharmacology. - 2013. - Vol. 168, № 2. - P. 283-295.Ling L., Maguire J.J., Davenport A.P. Endothelin-2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer // British journal of pharmacology. - 2013. - Vol. 168, № 2. - P. 283-295.Low S.K. et al. Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA // Human molecular genetics. - 2012. - dds020.Low S.K. et al. Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA // Human molecular genetics. - 2012. - dds020.Papassotiriou J. et al. Immunoluminometric assay for measurement of the C-terminal endothelin-1 precursor fragment in human plasma // Clinical chemistry. - 2006. - Vol. 52, № 6. - P. 1144-1151.Papassotiriou J. et al. Immunoluminometric assay for measurement of the C-terminal endothelin-1 precursor fragment in human plasma // Clinical chemistry. - 2006. - Vol. 52, № 6. - P. 1144-1151.Rahman T., Baker M., Hall D.H. et al. Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study // Journal of human hypertension. - 2008. - Vol. 22, № 4. - P. 282-288.Rahman T., Baker M., Hall D.H. et al. Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study // Journal of human hypertension. - 2008. - Vol. 22, № 4. - P. 282-288.Rankinen T. et al. Effect of endothelin 1 genotype on blood pressure is dependent on physical activity or fitness levels // Hypertension. - 2007. - Vol. 50, № 6. - P. 1120-1125.Rankinen T. et al. Effect of endothelin 1 genotype on blood pressure is dependent on physical activity or fitness levels // Hypertension. - 2007. - Vol. 50, № 6. - P. 1120-1125.Taillе C. et al. ETB receptor polymorphism is associated with airway obstruction // BMC pulmonary medicine. - 2007. - Vol. 7, № 1. - P. 5.Taillе C. et al. ETB receptor polymorphism is associated with airway obstruction // BMC pulmonary medicine. - 2007. - Vol. 7, № 1. - P. 5.Tatchum-Talom R. et al. Gender differences in hemodynamic responses to endothelin-1 // Journal of cardiovascular pharmacology. - 2000. - Vol. 36. - P. S102.Tatchum-Talom R. et al. Gender differences in hemodynamic responses to endothelin-1 // Journal of cardiovascular pharmacology. - 2000. - Vol. 36. - P. S102.Tiret L. et al. The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people // Hypertension. - 1999. - Vol. 33, № 5. - P. 1169-1174.Tiret L. et al. The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people // Hypertension. - 1999. - Vol. 33, № 5. - P. 1169-1174.Treiber F.A., Barbeau P., Harshfield G. et al. Endothelin-1 gene Lys198Asn polymorphism and blood pressure reactivity // Hypertension. - 2003. - Vol. 42, № 4. - P. 494-499.Treiber F.A., Barbeau P., Harshfield G. et al. Endothelin-1 gene Lys198Asn polymorphism and blood pressure reactivity // Hypertension. - 2003. - Vol. 42, № 4. - P. 494-499.Vadapalli S., Rani H.S., Sastry B.K.S. et al. Endothelin-1 and endothelial nitric oxide polymorphisms in idiopathic pulmonary arterial hypertension // International journal of molecular epidemiology and genetics. - 2010. - Vol. 1, № 3. - P. 208.Vadapalli S., Rani H.S., Sastry B.K.S. et al. Endothelin-1 and endothelial nitric oxide polymorphisms in idiopathic pulmonary arterial hypertension // International journal of molecular epidemiology and genetics. - 2010. - Vol. 1, № 3. - P. 208.Verweij N. et al. Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1 // Hypertension. - 2013. - Vol. 61, № 3. - P. 602-608.Verweij N. et al. Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1 // Hypertension. - 2013. - Vol. 61, № 3. - P. 602-608.Wiltshire S., Powell B.L., Jennens M. et al. Investigating the association between K198N coding polymorphism in EDN1 and hypertension, lipoprotein levels, the metabolic syndrome and cardiovascular disease // Human genetics. - 2008. - Vol. 123, № 3. - P. 307-313.Wiltshire S., Powell B.L., Jennens M. et al. Investigating the association between K198N coding polymorphism in EDN1 and hypertension, lipoprotein levels, the metabolic syndrome and cardiovascular disease // Human genetics. - 2008. - Vol. 123, № 3. - P. 307-313.Yanagisawa M. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells // Nature. - 1988. - Vol. 332, № 6163. - P. 411-415.Yanagisawa M. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells // Nature. - 1988. - Vol. 332, № 6163. - P. 411-415.Yasuda H. et al. Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension // Journal of human hypertension. - 2007. - Vol. 21, № 11. - P. 883-892.Yasuda H. et al. Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension // Journal of human hypertension. - 2007. - Vol. 21, № 11. - P. 883-892.Yasuno K. et al. Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk // Proceedings of the National Academy of Sciences. - 2011. - Vol. 108, № 49. - P. 19707-19712.Yasuno K. et al. Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk // Proceedings of the National Academy of Sciences. - 2011. - Vol. 108, № 49. - P. 19707-19712.

The authors declare that there are no conflicts of interest present.