<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">arthyper</journal-id><journal-title-group><journal-title xml:lang="ru">Артериальная гипертензия</journal-title><trans-title-group xml:lang="en"><trans-title>"Arterial’naya Gipertenziya" ("Arterial Hypertension")</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1607-419X</issn><issn pub-type="epub">2411-8524</issn><publisher><publisher-name>Antihypertensive League</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18705/1607-419X-2022-28-1-58-66</article-id><article-id custom-type="elpub" pub-id-type="custom">arthyper-2184</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНАЯ СТАТЬЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLE</subject></subj-group></article-categories><title-group><article-title>Факторы кардиометаболического риска и генетические полиморфизмы ренин-ангиотензиновой системы при различных метаболических фенотипах у лиц молодого возраста</article-title><trans-title-group xml:lang="en"><trans-title>Cardiometabolic risk factors and renin-angiotensin system polymorphisms in young individuals with various metabolic phenotypes</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0952-6856</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чулков</surname><given-names>В. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Chulkov</surname><given-names>V. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Чулков Василий Сергеевич — доктор медицинских наук, профессор кафедры факультетской терапии</p><p>ул. Воровского, д.64, Челябинск, 454092</p></bio><bio xml:lang="en"><p>Vasiliy S. Chulkov, MD, PhD, DSc, Professor, Department of Therapy</p><p>64 Borovskogo street, Chelyabinsk, 454092</p></bio><email xlink:type="simple">vschulkov@rambler.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7137-6935</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гаврилова</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Gavrilova</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гаврилова Елена Сергеевна—кандидат медицинских наук, доцент кафедры поликлинической терапии и клинической фармакологии</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Elena S. Gavrilova, MD, PhD, Associate Professor, Department of Outpatient Therapy and Clinical Pharmacology</p><p>Chelyabinsk</p></bio><email xlink:type="simple">helengavrilova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1948-8523</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чулков</surname><given-names>Вл. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Chulkov</surname><given-names>V. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Чулков Владислав Сергеевич — кандидат медицинских наук, доцент кафедры факультетской терапии</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Vladislav S. Chulkov, MD, PhD, Associate Professor, Department of Therapy</p><p>Chelyabinsk</p></bio><email xlink:type="simple">vlad.chulkov.1989@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6301-7630</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Панкова</surname><given-names>Е. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Pankova</surname><given-names>E. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Панкова Екатерина Дмитриевна — аспирант кафедры факультетской терапии</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Ekaterina D. Pankova, MD, Post-graduate Student, Department of Therapy</p><p>Chelyabinsk</p></bio><email xlink:type="simple">katerinachelsma@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2336-6411</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мартынов</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Martynov</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мартынов Сергей Александрович — соискатель кафедры факультетской терапии</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Sergey A. Martynov, MD, Department of Therapy</p><p>Chelyabinsk</p></bio><email xlink:type="simple">ftherapy2017@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6580-3857</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Манжос</surname><given-names>В. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Manzhos</surname><given-names>V. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Манжос Владислав Игоревич—студент 5-го курса лечебного факультета</p><p>Челябинск</p></bio><bio xml:lang="en"><p>Vladislav I. Manzhos, 5th year Student, Faculty of Medicine</p><p>Chelyabinsk</p></bio><email xlink:type="simple">mr.vladiman99@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Южно-Уральский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>South Ural State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>18</day><month>03</month><year>2022</year></pub-date><volume>28</volume><issue>1</issue><fpage>58</fpage><lpage>66</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Чулков В.С., Гаврилова Е.С., Чулков В.С., Панкова Е.Д., Мартынов С.А., Манжос В.И., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Чулков В.С., Гаврилова Е.С., Чулков В.С., Панкова Е.Д., Мартынов С.А., Манжос В.И.</copyright-holder><copyright-holder xml:lang="en">Chulkov V.S., Gavrilova E.S., Chulkov V.S., Pankova E.D., Martynov S.A., Manzhos V.I.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://htn.almazovcentre.ru/jour/article/view/2184">https://htn.almazovcentre.ru/jour/article/view/2184</self-uri><abstract><p>Возросшая распространенность ожирения и связанных с ним кардиометаболических заболеваний продолжает привлекать внимание во всем мире. Именно роль ренин-ангиотензиновой системы может быть связующим звеном между ожирением, с одной стороны, и сердечно-сосудистыми и метаболическими заболеваниями — с другой.</p><p>Цель исследования — провести комплексную оценку кардиометаболических факторов риска и полиморфизмов генов ренин-ангиотензиновой системы при различных метаболических фенотипах среди молодых людей.</p><sec><title>Материалы и методы</title><p>Материалы и методы. Общая выборка составила 251 человека, разделенных на четыре группы: группа 1 — метаболически здоровые лица с нормальным индексом массы тела (ИМТ) (n = 62); группа 2 — метаболически нездоровые лица с нормальным ИМТ (n = 57); группа 3 — лица с метаболически здоровой избыточной массой тела /ожирением (n = 16); группа 4 — лица с метаболически нездоровой избыточной массой тела/ожирением (n = 116). Все участники ответили на специально разработанную анкету. Были оценены антропометрические, клинические и биохимические параметры, полиморфизм A1166C гена рецептора ангиотензина II типа 1 (rs5186), полиморфизм M235T гена ангиотензиногена (rs699), полиморфизм T174M гена ангиотензиногена (rs4762), I/D полиморфизм гена ангиотензинпревращающего фермента (rs4340). Наиболее выраженные нарушения углеводного и липидного обмена на фоне более высоких уровней лептина и низких концентраций адипонектина в сыворотке крови были также выявлены у лиц молодого возраста с метаболически нездоровой избыточной массой тела/ожирением.</p></sec><sec><title>Результаты</title><p>Результаты. У лиц молодого возраста с метаболически нездоровой избыточной массой тела/ожирением выявлена более высокая частота сочетания ожирения с артериальной гипертензией в сочетании с более высокой частотой «мутантного» аллеля Т гена ангиотензиногена AGTM235T. Наиболее выраженные нарушения углеводного и липидного обмена на фоне более высоких уровней лептина и низких концентраций адипонектина в сыворотке крови были также выявлены у лиц молодого возраста с метаболически нездоровой избыточной массой тела/ожирением.</p></sec><sec><title> </title><p> </p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. The increased prevalence of obesity and associated cardiometabolic diseases attract attention worldwide. Renin-angiotensin system can link obesity and cardiovascular and metabolic diseases.</p></sec><sec><title>Objective</title><p>Objective. To access a comprehensive assessment of cardiometabolic risk factors and gene polymorphisms of the renin-angiotensin system in metabolic phenotypes among young individuals.</p></sec><sec><title>Design and methods</title><p>Design and methods. The sample consisted of 251 individuals, who were divided into four groups: group 1 — metabolically healthy individuals with normal body mass index (BMI) (n = 62); group 2 — metabolically unhealthy individuals with normal BMI (n = 57); group 3 — metabolically healthy overweight/obese individuals (n = 16); group 4— metabolically unhealthy overweight/ obese individuals (n = 116). All participants answered a questionnaire designed for this study. Anthropometric, clinical and biochemical parameters were assessed. The following polymorphisms were evaluated:, A1166C polymorphism of the angiotensin II type 1 receptor gene (rs5186), M235T polymorphism of the angiotensinogen gene (rs699), T174M polymorphism of the angiotensinogen gene (rs4762), I/D polymorphism of the angiotensinconverting enzyme gene (rs4340).</p></sec><sec><title>Results</title><p>Results. In young individuals with metabolically unhealthy overweight/ obesity, a higher frequency of coexistent abdominal obesity and hypertension was found in combination with a higher frequency of the allele T of AGT 235M/T. The greater differences in carbohydrate and lipid metabolism in combination with a higher serum levels of leptin and low serum concentrations of adiponectin were also found in young individuals with metabolically unhealthy overweight/obesity.</p></sec><sec><title> </title><p> </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>артериальная гипертензия</kwd><kwd>ренин-ангиотензиновая система</kwd><kwd>генные полиморфизмы</kwd><kwd>метаболические фенотипы</kwd><kwd>ожирение</kwd><kwd>инсулинорезистентность</kwd><kwd>дислипидемия</kwd><kwd>адипокины</kwd></kwd-group><kwd-group xml:lang="en"><kwd>hypertension</kwd><kwd>renin-angiotensin system</kwd><kwd>gene polymorphisms</kwd><kwd>metabolic phenotypes</kwd><kwd>obesity</kwd><kwd>insulin resistance</kwd><kwd>dyslipidemia</kwd><kwd>adipokines</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Hruby A, Hu FB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015;33(7):673–689. doi:10.1007/s40273-014-0243-x</mixed-citation><mixed-citation xml:lang="en">Hruby A, Hu FB. The epidemiology of obesity: a big picture. Pharmacoeconomics. 2015;33(7):673–689. doi:10.1007/s40273-014-0243-x</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">World Health Organization (WHO). Obesity and overweight. Geneve: WHO; 2021. Available from: https://www.who.int/newsroom/fact-sheets/detail/obesity-and-overweight [cited 2022 Jan 31].</mixed-citation><mixed-citation xml:lang="en">World Health Organization (WHO). Obesity and overweight. Geneve: WHO; 2021. Available from: https://www.who.int/newsroom/fact-sheets/detail/obesity-and-overweight [cited 2022 Jan 31].</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113(6):898–918. doi:10.1161/CIRCULATIONAHA.106.171016</mixed-citation><mixed-citation xml:lang="en">Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113(6):898–918. doi:10.1161/CIRCULATIONAHA.106.171016</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Чулков В. С., Ленец Е. А., Чулков В. С., Гаврилова Е.С., Минина Е. Е., Жданова О.В. Гендерные особенности патогенеза, профилактики и лечения метаболического синдрома. Артериальная гипертензия. 2020;26(4):371–382. doi:10.18705/1607-419X‑2020-26-4-371-382</mixed-citation><mixed-citation xml:lang="en">Chulkov VS, Lenets EA, Chulkov VS, Gavrilova ES, Minina EE, Zhdanova OV. Gender characteristics of the pathogenesis, prevention and treatment of metabolic syndrome. Arterial’naya Gipertenziya = Arterial Hypertension. 2020;26(4):371–382. doi:10.18705/1607-419X‑2020-26-4-371-382. In Russian.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Cabandugama PK, Gardner MJ, Sowers JR. The reninangiotensin-aldosterone system in obesity and hypertension: roles in the cardiorenal metabolic syndrome. Med Clin North Am. 2017; 101(1):129–137. doi:10.1016/j.mcna.2016.08.009</mixed-citation><mixed-citation xml:lang="en">Cabandugama PK, Gardner MJ, Sowers JR. The reninangiotensin-aldosterone system in obesity and hypertension: roles in the cardiorenal metabolic syndrome. Med Clin North Am. 2017; 101(1):129–137. doi:10.1016/j.mcna.2016.08.009</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lastra G, Sowers JR. Obesity and cardiovascular disease: role of adipose tissue, inflammation, and the reninangiotensinaldosterone system. Horm Mol Biol Clin Investig. 2013;15(2):49–57. doi:10.1515/hmbci‑2013-0025</mixed-citation><mixed-citation xml:lang="en">Lastra G, Sowers JR. Obesity and cardiovascular disease: role of adipose tissue, inflammation, and the reninangiotensinaldosterone system. Horm Mol Biol Clin Investig. 2013;15(2):49–57. doi:10.1515/hmbci‑2013-0025</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Thethi T, Kamiyama M, Kobori H. The link between the renin-angiotensin aldosterone system and renal injury in obesity and the metabolic syndrome. Curr Hypertens Rep. 2012;14(2):160–169. doi:10.1007/s11906-012-0245-z</mixed-citation><mixed-citation xml:lang="en">Thethi T, Kamiyama M, Kobori H. The link between the renin-angiotensin aldosterone system and renal injury in obesity and the metabolic syndrome. Curr Hypertens Rep. 2012;14(2):160–169. doi:10.1007/s11906-012-0245-z</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Pinheiro TA, Barcala-Jorge AS, Andrade JMO, Pinheiro TA, Ferreira ECN, Crespo TS et al. Obesity and malnutrition similarly alter the renin-angiotensin system and inflammation in mice and human adipose. J Nutr Biochem. 2017;48:74–82. doi:10.1016/j.jnutbio.2017.06.008</mixed-citation><mixed-citation xml:lang="en">Pinheiro TA, Barcala-Jorge AS, Andrade JMO, Pinheiro TA, Ferreira ECN, Crespo TS et al. Obesity and malnutrition similarly alter the renin-angiotensin system and inflammation in mice and human adipose. J Nutr Biochem. 2017;48:74–82. doi:10.1016/j.jnutbio.2017.06.008</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Szczepanska-Sadowska E, Rossi NF. Editorial: new trends in the renin-angiotensin-aldosterone system in cardiovascular disease. Front Pharmacol. 2021;12:790439. doi:10.3389/fphar.2021.790439</mixed-citation><mixed-citation xml:lang="en">Szczepanska-Sadowska E, Rossi NF. Editorial: new trends in the renin-angiotensin-aldosterone system in cardiovascular disease. Front Pharmacol. 2021;12:790439. doi:10.3389/fphar.2021.790439</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960–975. doi:10.1161/CIRCRESAHA.116.303587</mixed-citation><mixed-citation xml:lang="en">Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960–975. doi:10.1161/CIRCRESAHA.116.303587</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Wu CK, Lee JK, Lin LY, Huang YT, Hwang JJ, Lin CL et al. Renin- angiotensin system genes polymorphisms and long-term prognosis in Taiwanese patients with hypertension and coronary artery disease. Acta Cardiol Sin. 2013;29(1):28–36.</mixed-citation><mixed-citation xml:lang="en">Wu CK, Lee JK, Lin LY, Huang YT, Hwang JJ, Lin CL et al. Renin- angiotensin system genes polymorphisms and long-term prognosis in Taiwanese patients with hypertension and coronary artery disease. Acta Cardiol Sin. 2013;29(1):28–36.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Ji LD, Li JY, Yao BB, Cai XB, Shen QJ, Xu J. Are genetic polymorphisms in the renin-angiotensin-aldosterone system associated with essential hypertension? Evidence from genomewide association studies. J Hum Hypertens. 2017;31(11):695–698. doi:10.1038/jhh.2017.29</mixed-citation><mixed-citation xml:lang="en">Ji LD, Li JY, Yao BB, Cai XB, Shen QJ, Xu J. Are genetic polymorphisms in the renin-angiotensin-aldosterone system associated with essential hypertension? Evidence from genomewide association studies. J Hum Hypertens. 2017;31(11):695–698. doi:10.1038/jhh.2017.29</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Lelis DF, Pereira AC, Krieger JE, Mill JG, Santos SHS, Baldo MP. Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population. Arch Endocrinol Metab. 2019;63(4):402–410. doi:10.20945/2359-3997000000155</mixed-citation><mixed-citation xml:lang="en">Lelis DF, Pereira AC, Krieger JE, Mill JG, Santos SHS, Baldo MP. Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population. Arch Endocrinol Metab. 2019;63(4):402–410. doi:10.20945/2359-3997000000155</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации, VII пересмотр. Атеросклероз и дислипидемии. 2020;1(38):7–42. doi:10.34687/2219-8202.JAD.2020.01.0002</mixed-citation><mixed-citation xml:lang="en">Diagnostics and correction of lipid metabolism disorders in order to prevent and treat of atherosclerosis Russian recommendations VII revision. J Atheroscler Dyslipidem. 2020;1(38):7–42. doi:10.34687/2219-8202.JAD.2020.01.0002. In Russian.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33(16):2088–2097. doi:10.1093/eurheartj/ehs075</mixed-citation><mixed-citation xml:lang="en">van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33(16):2088–2097. doi:10.1093/eurheartj/ehs075</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Putnam K, Shoemaker R, Yiannikouris F, Cassis LA. The renin angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(6): H1219–30. doi:10.1152/ajpheart.00796.2011</mixed-citation><mixed-citation xml:lang="en">Putnam K, Shoemaker R, Yiannikouris F, Cassis LA. The renin angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(6): H1219–30. doi:10.1152/ajpheart.00796.2011</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Pacholczyk M, Ferenc T, Kowalski J, Adamczyk P, Chojnowski J, Ponikowska I. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol. 2013;32(8):435–442. doi:10.1089/dna.2013.2014</mixed-citation><mixed-citation xml:lang="en">Pacholczyk M, Ferenc T, Kowalski J, Adamczyk P, Chojnowski J, Ponikowska I. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol. 2013;32(8):435–442. doi:10.1089/dna.2013.2014</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Takakura Y, Yoshida T, Yoshioka K, Umekawa T, KogureA, Toda H et al. Angiotensinogen gene polymorphism (Met235Thr) influences visceral obesity and insulin resistance in obese Japanese women. Metabolism. 2006;55(6):819–824. doi:10.1016/j.metabol.2006.02.008</mixed-citation><mixed-citation xml:lang="en">Takakura Y, Yoshida T, Yoshioka K, Umekawa T, KogureA, Toda H et al. Angiotensinogen gene polymorphism (Met235Thr) influences visceral obesity and insulin resistance in obese Japanese women. Metabolism. 2006;55(6):819–824. doi:10.1016/j.metabol.2006.02.008</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Pan YH, Wang M, Huang YM, Wang YH, Chen YL, Geng LJ et al. ACE gene I/D polymorphism and obesity in 1,574 patients with type 2 diabetes mellitus. Dis Markers. 2016;2016:7420540. doi:10.1155/2016/7420540</mixed-citation><mixed-citation xml:lang="en">Pan YH, Wang M, Huang YM, Wang YH, Chen YL, Geng LJ et al. ACE gene I/D polymorphism and obesity in 1,574 patients with type 2 diabetes mellitus. Dis Markers. 2016;2016:7420540. doi:10.1155/2016/7420540</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Motawi TK, Shaker OG, Shahin NN, Ahmed NM. Angiotensinconverting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study. Nutr Metab (Lond). 2016;13:68. doi:10.1186/s12986-016-0127-5</mixed-citation><mixed-citation xml:lang="en">Motawi TK, Shaker OG, Shahin NN, Ahmed NM. Angiotensinconverting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study. Nutr Metab (Lond). 2016;13:68. doi:10.1186/s12986-016-0127-5</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
