arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2024-2446OXDWFParthyper-2446Research ArticleСтатьиArticlesГенетические детерминанты уровня ангиотензинпревращающего фермента (данные полногеномных исследований)Genetic determinants of angiotensin-converting enzyme levels (data from genome-wide studies)https://orcid.org/0000-0002-6129-0625КамышниковаЛ. А.KamyshnikovaL. A.

Камышникова Людмила Александровна — кандидат медицинских наук, доцент, доцент кафедры факультетской терапии медицинского института

ул. Победы, 85, Белгород, 308015

Lyudmila A. Kamyshnikova - MD, PhD, Associate Professor, the Department of Faculty Therapy of the Medical Institute

85 Pobedy St., Belgorod, 308015

kamyshnikova@bsu.edu.ruhttps://orcid.org/0000-0002-6395-1626ЕфремоваО. А.EfremovaO. A.

Ефремова Ольга Алексеевна — доктор медицинских наук, профессор, заведующая кафедрой факультетской терапии медицинского института

ул. Победы, 85, Белгород, 308015

85 Pobedy St., Belgorod, 308015

efremova@bsu.edu.ruhttps://orcid.org/0000-0002-4053-386XФентисовВ. В.FentisovV. V.

Фентисов Виталий Владимирович — кандидат медицинских наук, доцент кафедры факультетской терапии медицинского института

ул. Победы, 85, Белгород, 308015

85 Pobedy St., Belgorod, 308015

fentisov@bsu.edu.ruhttps://orcid.org/0000-0002-8331-6873БолховитинаО. А.BolkhovitinaO. A.

Болховитина Ольга Александровна — кандидат медицинских наук, доцент кафедры факультетской терапии медицинского института

ул. Победы, 85, Белгород, 308015

85 Pobedy St., Belgorod, 308015

bolkhovitina_o@bsu.edu.ruhttps://orcid.org/0000-0003-1254-6134ЧурносовМ. И.ChurnosovM. I.

Чурносов Михаил Иванович — доктор медицинских наук, профессор, заведующий кафедрой медико-биологических дисциплин медицинского института

ул. Победы, 85, Белгород, 308015

85 Pobedy St., Belgorod, 308015

churnosov@bsu.edu.ruФГАОУ ВО «Белгородский государственный национальный исследовательский университет»РоссияBelgorod State National Research UniversityRussian Federation202422112024306537–552Copyright © Камышникова Л.А., Ефремова О.А., Фентисов В.В., Болховитина О.А., Чурносов М.И., 20252025Камышникова Л.А., Ефремова О.А., Фентисов В.В., Болховитина О.А., Чурносов М.И.Kamyshnikova L.A., Efremova O.A., Fentisov V.V., Bolkhovitina O.A., Churnosov M.I.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/2446

Ангиотензинпревращающий фермент (АПФ) является ключевым ферментом ренин-ангиотензинальдостероновой системы (РААС) и имеет большое значение в раннем прогнозировании, диагностике и лечении заболеваний сердечно-сосудистой системы (ССС), почек, COVID‑19. Среди факторов, определяющих уровень АПФ в организме, важную роль играют генетические факторы. Понимание роли конкретных генетических детерминант, связанных с уровнем АПФ, может иметь практическое значение, так как позволит использовать эти генетические детерминанты в качестве маркеров высокого уровня АПФ и, соответственно, маркеров высокого риска развития заболеваний, патогенетически связанных с АПФ.Цель исследования — изучить генетические детерминанты уровня/активности АПФ по данным полногеномных ассоциированных исследований (GWAS).Материал и методы. Поиск публикаций был выполнен в каталоге GWAS за период с 2010 до 2024 года по ключевым словам: ангиотензинпревращающий фермент (angiotensin-converting enzyme), АПФ (ACE).Результаты. На настоящий момент выполнено 7 GWAS-исследований, в результате которых выявлено 14 полиморфных локусов, ассоциированных с уровнем/активностью АПФ, среди которых наибольшее количество SNP находится в двух участках генома — 17q23.3 (8 SNP) и 9q34.2 (4 SNP). Из них 79 % (11 SNP) проявляют выраженные плейотропные эффекты и являются GWAS-значимыми по отношению к показателям, характеризующим липидный и углеводный обмен, иммунный статус, функциональную активность печени и почек, уровень артериального давления, а также эти полиморфизмы ассоциированы с рядом болезней: ССС, COVID‑19, болезнью Альцгеймера, венозной тромбоэмболией. Наиболее выраженные плейотропные эффекты по GWAS-данным проявляют полиморфизмы: rs507666, rs495828, rs8176746 гена ABO (9q34.2). По данным полногеномных исследований, со всеми 14 локусами, связанными с уровнем/активностью АПФ, находятся в неравновесии по сцеплению полиморфизмы (более 60 SNP), которые ассоциированы с различными многочисленными признаками, связанными с обменом липидов/углеводов, иммунными и сосудистыми реакциями, функциональным состоянием печени/почек, межклеточными взаимодействиями, свертывающей/противосвертывающей системой, а также с сердечно-сосудистыми заболеваниями, сахарным диабетом 2‑го типа, COVID‑19 и другими.Заключение. Уровень/активность АПФ генетически детерминированы полиморфизмами преимущественно регионов генома 17q23.3 и 9q34.2, которые проявляют выраженные плейотропные фенотипические эффекты.

Angiotensin converting enzyme (ACE) is a key enzyme of the renin-angiotensin- aldosterone system. It plays an important role in the early prognosis, diagnosis and treatment of diseases of the cardiovascular system (CVS), kidneys, and COVID‑19. Among the factors determining the ACE level, genetic factors play an important role. Understanding the role of specific genetic determinants associated with ACE levels is important, as these genetic determinants can be potentially used as markers of high ACE levels and, accordingly, markers of high risk of developing ACE-associated diseases.Objective. To study the genetic determinants of ACE levels/activity using data genome-wide association search (GWAS).Design and methods. A search for publications was performed in the GWAS catalog for the period from 2010 to 2024 using the keywords: angiotensin-converting enzyme, ACE.Results. To date, 7 GWAS studies have been carried out, resulting in identification of 14 polymorphic loci associated with the level / activity of ACE. Among them, the largest number of SNPs is located in two regions of the genome — 17q23.3 (8 SNPs) and 9q34.2 (4 SNPs). Out of these, 79 % (11 SNPs) exhibit pronounced pleiotropic effects and are GWAS-significant in relation to indicators of lipid and carbohydrate metabolism, immune status, are associated with the functional activity of the liver and kidneys, blood pressure levels. These polymorphisms are associated with a number of diseases: CVS, COVID‑19, Alzheimer’s disease, venous thromboembolism. According to GWAS data, the most pronounced pleiotropic effects are exhibited by polymorphisms: rs507666, rs495828, rs8176746 of the ABO gene (9q34.2). According to genome-wide studies with all 14 loci associated with the level / activity of ACE, polymorphisms (more than 60 SNPs) are in linkage disequilibrium, which are associated with various numerous traits associated with lipid / carbohydrate metabolism, immune / vascular reactions, functional state of the liver and kidneys, intercellular interactions, coagulation / anticoagulation system, etc., as well as with cardiovascular diseases, type 2 diabetes mellitus, COVID‑19, etc.Conclusions. The level / activity of ACE is genetically determined by polymorphisms of predominantly genome regions 17q23.3 and 9q34.2, which exhibit pronounced pleiotropic phenotypic effects.

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