arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2022-28-1-33-45arthyper-2126Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLEПолигенный анализ наследственной предрасположенности к эссенциальной гипертензииPolygenic analysis of genetic susceptibility to essential hypertensionhttps://orcid.org/0000-0002-9918-6962ТимашеваЯ. Р.TimashevaY. R.

Тимашева Янина Римовна—кандидат медицинских наук, старший научный сотрудник Лаборатории физиологической генетики Института биохимии и генетики, обособленного структурного подразделения ФГБНУ «Уфимский федеральный исследовательский центр» РАН; доцент кафедры медицинской генетики и фундаментальной медицины ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России

пр. Октября, д. 71, г. Уфа, 450054

Yanina R. Timasheva, MD, PhD, Senior Scientist, Laboratory of Physiological Genetics, Institute of Biochemistry and Genetics— Subdivision of the Ufa Federal Research Centre of Russian Academy of Sciences; Associate Professor, Department of Medical Genetics and Fundamental Medicine, Bashkir State Medical University

71 October avenue, Ufa, 450054

ianina_t@mail.ruhttps://orcid.org/0000-0002-4962-7344ГерасимоваК. А.GerasimovaK. A.

Герасимова Кристина Александровна — магистр

Уфа

Kristina A. Gerasimova, Master’s Student

Ufa

kr1s.gerasimova@yandex.ruhttps://orcid.org/0000-0001-6928-648XТуктароваИ. А.TuktarovaI. A.

Туктарова Ильсияр Авхатовна—старший научный сотрудник Лаборатории физиологической генетики Института биохимии и генетики, обособленного структурного подразделения

Уфа

Ilsiyar A. Tuktarova, MD, PhD, Senior Scientist, Laboratory of Physiological Genetics, Institute of Biochemistry and Genetics— Subdivision

Ufa

iltuk@mail.ruhttps://orcid.org/0000-0002-1219-3458ЭрдманВ. В.ErdmanV. V.

Эрдман Вера Викторовна — старший научный сотрудник Лаборатории физиологической генетики Института биохимии и генетики, обособленного структурного подразделения

Уфа

Vera V. Erdman, MD, PhD, Senior Scientist, Laboratory of Physiological Genetics, Institute of Biochemistry and Genetics— Subdivision

Ufa

danivera@mail.ruhttps://orcid.org/0000-0001-8823-8678НасибуллинТ. Р.NasibullinT. R.

Насибуллин Тимур Русланович — старший научный сотрудник Лаборатории физиологической генетики Института биохимии и генетики, обособленного структурного подразделения

Уфа

Timur R. Nasibullin, MD, PhD, Senior Scientist, Laboratory of Physiological Genetics, Institute of Biochemistry and Genetics— Subdivision

Ufa

nasibullintr@yandex.ruФедеральное государственное бюджетное научное учреждение «Уфимский федеральный исследовательский центр» Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего образования «Башкирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияUfa Federal Research Center; Bashkir State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Башкирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииRussian FederationBashkir State Medical UniversityRussian FederationФедеральное государственное бюджетное научное учреждение «Уфимский федеральный исследовательский центр» Российской академии наукRussian FederationUfa Federal Research CenterRussian Federation2022110320222813345Copyright © Тимашева Я.Р., Герасимова К.А., Туктарова И.А., Эрдман В.В., Насибуллин Т.Р., 20222022Тимашева Я.Р., Герасимова К.А., Туктарова И.А., Эрдман В.В., Насибуллин Т.Р.Timasheva Y.R., Gerasimova K.A., Tuktarova I.A., Erdman V.V., Nasibullin T.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/2126

Цель исследования состояла в изучении молекулярно-генетических основ предрасположенности к эссенциальной гипертензии (ЭГ) на основании полигенного анализа генов, кодирующих компоненты ренин-ангиотензин-альдостероновой системы (РААС).

Материалы и методы

Материалы и методы. Проводилось генотипирование 346 пациентов с ЭГ и 377 представителей контрольной группы, русских и татар по этнической принадлежности, по маркерам генов ренина REN (rs2368564, G83A, MboI), ангиотензиногена AGT (rs4762, T174M), рецептора ангиотензина II типа 1 AGTR1 (rs5186, A1166C), химазы 1 CMA1 (rs1800875, G 1903A) и ангиотензинпревращающего фермента ACE (rs1799752, I/D).

Результаты

Результаты. Обнаружено, что вариант ACE rs1799752 значимо ассоциирован с риском ЭГ в группе татар (PBonf = 0,003) и в общей выборке без деления на этнические группы (PBonf = 4,09х10–5). Идентифицировано 12 сочетаний генотипов и/или аллелей полиморфных вариантов генов РААС, значимо ассоциированных с ЭГ в группе татар и 6 — в общей выборке. Наиболее высокий риск заболевания у мужчин-татар ассоциирован с сочетанием REN rs2368564*Т + AGTR1 rs5186*С/А + ACE rs1799752*D (OR = 16,64, PBonf = 0,001), а в общей выборке исследования — с сочетанием генотипа REN rs2368564*T/C и аллеля CMA1 rs1800875*G (OR = 2,37, PBonf = 0,045).

Заключение

Заключение. В результате проведенного исследования обнаружено, что у мужчин русской и татарской этнической принадлежности риск ЭГ значимо ассоциирован с инсерционно-делеционным полиморфизмом гена ACE, а результаты полигенного анализа свидетельствуют об ассоциации риска развития заболевания с сочетаниями генотипов и аллелей генов REN (rs2368564), AGTR1 (rs5186), ACE (rs1799752) и CMA1 (rs1800875).

Objective

Objective. To investigate the molecular mechanism underlying genetic susceptibility to essential hypertension (EH) using polygenic analysis of renin-angiotensin-aldosterone system (RAAS).

Design and methods

Design and methods. Genotyping of renin (REN, rs2368564), angiotensinogen (AGT, rs4762), angiotensin II receptor type 1 (AGTR1, rs5186), chymase 1 (CMA1, rs1800875) and angiotensin-converting enzyme (ACE, rs1799752) polymorphic variants was performed in 346 patients with EH and 377 controls, Russians and Tatars by ethnic origin.

Results

Results. ACE rs1799752polymorphism was significantly associated with EH risk in Tatars (PBonf = 0,003) and in the total study group (PBonf = 4,09 x 10–5). Polygenic approach identified 12 genotypes and/or alleles combinations of RAAS genes polymorphisms, significantly associated with EH in the Tatars, and 6 patterns associated with EH in the total study group. The highest risk of disease in Tatar men was associated with REN rs2368564*T + AGTR1 rs5186*C/A + ACE rs1799752*D combination (OR = 16,64, PBonf = 0,001), in the total group — with REN rs2368564*T/C + CMA1 rs1800875*G combination (OR = 2,37, PBonf = 0,045).

Conclusions

Conclusions. Our findings indicate that EH risk in men of Russian and Tatar ethnicity is significantly associated with ACE rs1799752 polymorphism, and the results of polygenic analysis demonstrate an association of the disease risk with genotype/allele combinations of polymorphic variants in REN (rs2368564), AGTR1 (rs5186), ACE (rs1799752), and CMA1 (rs1800875) genes.

 

 

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