Genetic predictors of chronic heart failure in obese patients
https://doi.org/10.14341/omet9667
Abstract
BACKGROUND: the study of molecular genetic markers and pathogenetic mechanisms of neurohormonal activation, as well as their importance in the formation of heart failure in obesity, is an urgent problem of modern medicine, the solution of which will allow effective prevention of cardiovascular complications, optimize treatment and improve the prognosis of obese patients.
AIMS: search for genetic markers presumably involved in the pathogenesis of secondary diastolic heart failure in patients with obesity.
MATERIALS AND METHODS: PCR-diagnostics of whole blood of 104 patients with obesity was carried out, which were divided into 2 groups, depending on the presence of diastolic heart failure. The following candidate genes were analyzed: angiotensinogen AGT gene (C521T and T704C), angiotensin II receptor gene of the first type AGTR1 (A1166C), angiotensin II receptor gene of the second type AGTR2 (G1675A), aldosterone synthase gene CYP11B2 (C (-344) T).
RESULTS: It is shown that the development of secondary diastolic heart failure in obese individuals of both sexes is associated with the mutation of the aldosterone synthase gene CYP11B2, namely, with the replacement of the C allele at the -344 position by the T allele and the presence of the T / T genotype. The relative risk of developing the disease with the T / T genotype was 5.93 times higher in men (p = 0.008) and 4.57 times in women (p = 0.014). For men, the mutation of the angiotensinogen AGT gene, namely the replacement of the allele C at position 521 by the T allele, is important. At the same time, the relative risk of development of SDS in the T / T genotype is increased by 4.26 times (p = 0.039). Mutations of the genes of the angiotensin II receptor of the first type AGTR1 (A1166C) and the angiotensin II receptor of the second type AGTR2 (G1675A) are not associated with the development of diastolic heart failure in obese patients.
CONCLUSIONS: The data presented can be used to stratify the risk of secondary heart failure in obese individuals.
About the Authors
Alfred R. BogdanovFederal Research Centre of nutrition, biotechnology and food safety; Pirogov Russian National Research Medical University
Russian Federation
MD, PhD; Head of Cardiovascular Pathology Department; Associate Professor of the Department of Gastroenterology and Dietetics
Svetlana A. Derbeneva
Federal Research Centre of nutrition, biotechnology and food safety
Russian Federation
PhD, Senior Researcher of the Department of Cardiovascular Pathology
Olga O. Cherniak
Federal Research Centre of nutrition, biotechnology and food safety
Russian Federation
PhD in biology, research associate of the Laboratory of Clinical Biochemistry and Immunology.
Alexandra A. Bogdanova
City Clinical Hospital No. 1 named after. N.I. Pirogov of Moscow Health Department
Russian Federation
MD, PhD, head of the Functional Diagnostics Department
Kamilat M. Gapparova
Federal Research Centre of nutrition, biotechnology and food safety
Russian Federation
MD, PhD, Head of the Department of Preventive and Rehabilitation Dietetics
Olga N. Grigorian
Federal Research Centre of nutrition, biotechnology and food safety
Russian Federation
MD, PhD, Leading Researcher of the Department of Preventive and Rehabilitation Dietetics
References
1. Залетова Т.С. Патофизиология ожирения и ассоциированной с ним сердечно-сосудистой патологии // Вопросы диетологии. – 2014. – Т.4. – №1. – C.29-33. [Zaletova TS. Pathophysiology of obesity and associated cardiovascular pathology. Voprosy dietologii. 2014;4(1):29-33. (In Russ.)]
2. Погожева А.В., Батурин А.К., Егоренкова Н.Е., и др. Оценка факторов риска сердечно-сосудистых заболеваний у мужчин и женщин / Сборник тезисов Научно-практической конференции с международным участием «Профилактика 2015»; Москва, 11 июня 2015 г. - Кардиоваскулярная терапия и профилактика; Специальный выпуск. 2015;14 (Июнь) — М.: Силицея-Полиграф, 2015. — С.14b–15a. [Pogozheva AV, Baturin AK, Egorenkova NE, et al. Otsenka faktorov riska serdechno-sosudistykh zabolevanii u muzhchin i zhenshchin. In: Proceedings of the scientific and practical conference with the international participation «Prevention 2015». - Kardiovaskulârnaâ terapiâ i profilaktika; Special release. 2015;14 (June); Moscow, 15-16 June 2015. Moscow: Silicea-Poligraf; 2015. P.14b–15a. (In Russ.)]
3. Лапик И.А., Гаппарова К.М., Чехонина Ю.Г., и др. Современные тенденции развития нутригеномики ожирения // Вопросы питания. – 2016. – Т.85. – №6. – C.6-13. [Lapik IA, Gapparova KM, Chekhonina YuG, et al. Current trends in nutrigenomics of obesity. Voprosy pitaniâ. 2016; 85(6):6-13. (In Russ.)]
4. Березикова Е.Н. Клинико-генетические и нейрогормональные механизмы развития ишемического ремоделирования, апоптоза миокарда и сердечной недостаточности: инновационная стратегия персонализированной диагностики, профилактики и лечения. Диссертация на соискание степени доктора мед. наук. – Томск; 2014. [Berezikova EN. Kliniko-geneticheskie i neirogormonal'nye mekhanizmy razvitiya ishemicheskogo remodelirovaniya, apoptoza miokarda i serdechnoi nedostatochnosti: innovatsionnaya strategiya personalizirovannoi diagnostiki, profilaktiki i lecheniya. [dissertation] Tomsk; 2014. (In Russ.)] Доступно по: http://docplayer.ru/43228271-Berezikova-ekaterina-nikolaevna.html. Ссылка активна на 07.04.2019.
5. Арутюнов Г.П. Терапия ХСН. Всегда ли детерминирован выбор первого препарата? // Русский медицинский журнал. – 2006. – Т.14. – №2. – C.137-142. [Arutyunov GP. Terapiya KhSN. Vsegda li determinirovan vybor pervogo preparata? Russkij medicinskij žurnal. 2006;14(2):137-142. (In Russ.)]
6. Vogt B, Bochud M, Burnier M. The Association of Aldosterone With Obesity-Related Hypertension and the Metabolic Syndrome. Semin Nephrol. 2007;27(5):529-537. doi: 10.1016/j.semnephrol.2007.07.009
7. Ruano M, Silvestre V, Castro R, et al. Morbid Obesity, Hypertensive Disease and the Renin-Angiotensin-Aldosterone Axis. Obes Surg. 2005;15(5):670-676. doi: 10.1381/0960892053923734
8. Li X, Li Q, Wang Y, et al. AGT gene polymorphisms (M235T, T174M) are associated with coronary heart disease in a Chinese population. J Renin-Angiotensin-Aldosterone Syst. 2013;14(4):354-359. doi: 10.1177/1470320312452029
9. Мартынович Т.В., Акимова Н.С., Федотов Э.А., Шварц Ю.Г. Анализ генетических факторов у больных хронической сердечной недостаточностью // Международный медицинский журнал. – 2014. – Т.20. – №1. – C.21-29. [Martynovich TV, Akimova NS, Fedotov EA, Shvarts YuG. Analysis of genetic factors in patients with chronic heart failure. Meždunarodnyj medicinskij žurnal. 2014;20(1):21–29. (In Russ.)]
10. Куба А.А., Никонова Ю.М., Феликсова О.М., и др. Ассоциация генетического полиморфизма гена эндотелиальной синтазы оксида азота с сердечно-сосудистой патологией // Современные проблемы науки и образования. – 2015. – № 3. [Kuba AA, Nikonova JM, Feliksova OM et al. Association of the polymorphism of endothelial nitric oxide synthase and cardiovascular diseases. Modern problems of science and education. 2015;(3). (In Russ.)] doi: 10.17513/spno.2015.3
11. Муженя Д.В., Ашканова Т.М., Калакуток К.Б., и др. Ассоциация Met235Thr полиморфизма гена ангиотензиногена (АGT) и А1166С аллели гена рецептора I типа ангиотензиногена-2 (AGT2R1) с сердечно-сосудистыми заболеваниями (ССЗ) у жителей Республики Адыгея // Вестник Адыгейского государственного университета. – 2011. – №2. [Muzhenya DV, Ashkanova TM, Kalakutok KB, et al. Association Met-235Thr of AGT gene polymorphism and A1166C alleles of a receptor gene of type I angiotenzinogene-2 (AGT2R1) with cardiovascular diseases at inhabitants of the Adygheya Republic. Vestnik Adygejskogo gosudarstvennogo universiteta. 2011;2. (In Russ.)]
12. Mustafina OE, Nasibullin TR, Khusnutdinova EK. Association of the T174M polymorphism of the angiotensinogen gene with essential hypertension in Russians and Tatars from Bashkortostan. Mol Biol (Mosk). 2002;36(4):599-604. doi: 10.1023/A:1019835923458 PMID: 12173461
13. Pei Y, Scholey J, Thai K, Suzuki M, Cattran D. Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients. J Clin Invest. 1997;100(4):814-820. doi: 10.1172/JCI119596
14. Schelleman H, Klungel OH, Witteman JCM, et al. Angiotensinogen M235T polymorphism and the risk of myocardial infarction and stroke among hypertensive patients on ACE-inhibitors or β-blockers. Eur J Hum Genet. 2007;15(4):478-484. doi: 10.1038/sj.ejhg.5201789
15. Kobashi G, Hata A, Ohta K, et al. A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene. J Hum Genet. 2004;49(4):182-186. doi: 10.1007/s10038-004-0129-4
16. Kuznetsova T, Staessen JA, Brand E, et al. Sodium excretion as a modulator of genetic associations with cardiovascular phenotypes in the European Project on Genes in Hypertension. J Hypertens. 2006;24(2):235-242. doi: 10.1097/01.hjh.0000194115.89356.bd
17. Yamada T, Horiuchi M, Dzau VJ. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci. 1996;93(1):156-160. doi: 10.1073/pnas.93.1.156
18. Casiglia E, Tikhonoff V, Mazza A, et al. C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: A population-based study. J Hypertens. 2005. doi: 10.1097/01.hjh.0000183119.92455.a7
19. Paillard F, Chansel D, Brand E, et al. Genotype-Phenotype Relationships for the Renin-Angiotensin-Aldosterone System in a Normal Population. Hypertension. 1999;34(3):423-429. doi: 10.1161/01.HYP.34.3.423
Supplementary files
Review
For citations:
Bogdanov A.R., Derbeneva S.A., Cherniak O.O., Bogdanova A.A., Gapparova K.M., Grigorian O.N. Genetic predictors of chronic heart failure in obese patients. Obesity and metabolism. 2019;16(1):39-46. (In Russ.) https://doi.org/10.14341/omet9667

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).