Significance of aldosterone synthase gene (CYP11B2) polymorphism as a component of the renin-angiotensin-aldosterone system in the pathogenesis of myocardial hypertrophy in hypertension: literature review and own experience


Keywords: aldosterone synthase, genetic polymorphism, aldosterone, RAAS, hypertension, left ventricular hypertrophy

Abstract

Aldosterone synthase gene is one of the candidate genes responsible for the effects of aldosterone. In particular, there are some evidences concerning the influence of this gene on the myocardial remodeling in hypertension. The analysis and summary of the results of published researches devoted to the study of aldosterone synthase gene (CYP11B2) polymorphism and its importance in the processes of hypertensive myocardial remodeling are presented in the article. Pub Med and EMBASE databases were used. The results of the study of CYP11B2 polymorphism within the framework of the research work at the Department of Internal Medicine of Medical Faculty №2 are presented in the article. The aim of the study is to study the importance of polymorphism of aldosterone synthase gene in the pathogenesis and clinic of hypertension. It has been shown that among both, hypertensive and males, residents of Podillia region of Ukraine, the overwhelming majority were carriers of TC polymorphism of CYP11B2 gene. These data are in the agreement with the previous studies in the European population.

References

1. Dolzhenko, M., Dosenko, V., & Lobach, L. (2017). Polimorfizm hena aldosteron syntetazy (CYP11b2) i pokaznyky diastolichnoi funktsii livoho shlunochka u patsiientiv z ishemichnoiu khvoroboiu sertsia ta postinfarktnym kardiosklerozom (analiz danykh patsiientiv homozyhot) [Polymorphism of the aldosterone synthetase gene (CYP11b2) and left ventricular diastolic function in patients with coronary heart disease and post-infarction cardiosclerosis (analysis of patients with homozygotes)]. Liky Ukrainy – Medications of Ukraine, 3 (32), 71–76.

2. Dolzhenko, M. M., Dosenko, V. Ye., & Lobach, L. Ye. (2017). Polimorfizm hena aldosteron syntetazy (CYP11b2) ta strukturni pokaznyky livoho shlunochka v patsiientiv z IKhS, postinfarktnym kardiosklerozom [Polymorphism of the aldosterone synthetase gene (CYP11b2) and structural left ventricular parameters in patients with coronary artery disease, post-infarction cardiosclerosis]. Zaporizkyi medychnyi zhurnal – Zaporozhye Medical Journal, 6 (105), 716–725.

3. Zhebel, V. M., Starzhynska, O. L., Hefter, Yu. O., Blanar, O. L., Palii, I. K., & Shevchuk, O. K. (2009). Henotyp retseptora do anhiotenzynu II 1-ho typu yak faktor vplyvu na strukturu ta funktsiiu miokarda u khvorykh na hipertonichnu khvorobu [Genotype of the receptor to angiotensin II type 1 as a factor influencing the structure and function of the myocardium in patients with hypertension]. Arterialnaya gipertenziya – Arterial hypertension, 1 (3), 54–58.

4. Zhebel, V. M., Starzhynska, O. L., & Hefter, Yu. O. (2006). Polimorfizm hena retseptora anhiotenzynu II u khvorykh na hipertonichnu khvorobu riznykh stadii yak faktor vplyvu na strukturu ta funktsiiu miokardu [Polymorphism of the angiotensin II receptor gene in patients with hypertonic disease of different stages as a factor affecting the structure and function of the myocardium]. Ukrainskyi kardiolohichnyi zhurnal. Materialy mizhnarodnoho forumu “Kardiolohiia vchora, sohodni, zavtra” – Ukrainian Cardiology Magazine. Materials of the International Forum “Cardiology Yesterday, Today, Tomorrow”, 54–58.

5. Petiunina, O. V. (2017). Asotsiatsiia infarktu miokarda z pidiomom sehmenta ST z polimorfizmom A1166S hena retseptora do anhiotenzynu II pershoho typu [Association of myocardial infarction with the rise of the ST segment with A1166C polymorphism of the receptor gene to angiotensin II of the first type]. Bukovynskyi medychnyi visnyk – Bukovinsky medical bulletin, 3 (83), 44–50.

6. Franchuk, S. V., & Zhebel, V. M. (2011). Strukturno-funktsionalni osoblyvosti sertsia pry uspadkuvanni riznykh variantiv hena retseptora anhiotenzynu II pershoho typu u zhinok, yaki perenesly infarkt miokarda ta mozkovyi insult na tli hipertonichnoi khvoroby [The structural-functional features of the heart when inheriting various variants of the gene of the angiotensin II receptor of the first type in women who suffered a myocardial infarction and a cerebral stroke against a background of hypertension]. Visnyk morfolohii – Reports of Morphology, 17 (3), 598–603.

7. Tseluiko, V. Y., & Yakovleva, L. M. (2013). Henetychni aspekty arterialnoi hipertenzii u khvorykh na ishemichnu khvorobu sertsia [Genetic aspects of arterial hypertension in patients with coronary heart disease]. Arteryalnaia hypertenzyia – – Arterial hypertension, 5 (31), 16–20.

8. Yahontov, D. A., Derisheva, D. A., & Gulyaeva, L. F. (2014). Polimorfizm gena aldosteronsintazy u bolnyh arterialnoj gipertenziej v sochetanii s ishemicheskoj boleznyu serdca pri razlichnoj masse miokarda levogo zheludochka [Polymorphism of the aldosterone synthase gene in patients with arterial hypertension in combination with coronary heart disease with a different mass of the myocardium of the left ventricle]. Sistemnye gipertenzii – Systemic hypertension, 1, 16–20.

9. Adam, O., Zimmer, C., Hanke, N., Hartmann, R. W., Klemmer, B., Böhm, M. & Laufs, U. (2015). Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. Journal of Molecular and Cellular Cardiology, 85, 140–150. doi: 10.1016/j.yjmcc.2015.05.019.

10. Baird, T., Palmer, B., Frampton, C., Yandle, T., Skelton, L., Richards, A., & Cameron, V. (2007). Association of the aldosterone synthase gene C-344T polymorphism with risk factors and survival in a post-myocardial infarction cohort. Journal of Human Hypertension, 21 (3), 256–258. DOI: 10.1038/sj.jhh.1002130.

11. Briet, M., & Schiffrin, E. L. (2012). Vascular Actions of Aldosterone. Journal of Vascular Research, 50, 89–99. doi: 10.1159/000345243.

12. Briet, M., Barhoumi, T., Mian, M.O.R., Coelho, S. C., Ouerd, S., Rautureau, Y. & Schiffrin, E. L. (2016). Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors. Hypertension, 67 (5), 897–905. doi: 10.1161/HYPERTENSIONAHA.115.07074.

13. Caproş, N., Barbacar, N., Istrati, V., & Branişte, T. (2013). Aspects of the molecular-genetic profile in patients with ischemic heart disease. Rev. Med. Chir. Soc. Med. Nat. Iasi, 117 (1), 78–82. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24505896.

14. Catena, C., Colussi, G., Martinis, F., Novello, M., & Sechi, L. A. (2017). Microalbuminuria and plasma aldosterone levels in nondiabetic treatment-naïve patients with hypertension. J. Hypertens., 35 (12), 2510–2516. doi: 10.1097/HJH.0000000000001476.

15. Clerico, A., & Emdin, M. (2004). Endocrine paradox in heart failure: resistance to biological effects of cardiac natriuretic hormones. Clinical Chemistry, 50 (12), 2465–2467. DOI: 10.1373/clinchem.2004.041533.

16. Díez, J., & Frohlich, E. D. (2010). A translational approach to hypertensive heart disease. Hypertension, 55 (1), 1–8.

17. Emdin, M., Fatini, C., Mirizzi, G., Poletti, R., Borrelli, C., Prontera, C. … Vergaro, G. (2015). Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible? Clinica Chimica Acta, 443, 85–93. doi: 10.1016/j.cca.2014.10.031.

18. Essick, E., & Flora, S. (2011). Cardiac Hypertrophy and Fibrosis in the Metabolic Syndrome: A Role for Aldosterone and the Mineralocorticoid Receptor. International Journal of Hypertension, 264–273. DOI: 10.4061/2011/346985.

19. Funder, J. W. (2013). Primary aldosteronism and low-renin hypertension: a continuum? Nephrol Dial Transplant., 28 (7), 1625–1627. doi: 10.1093/ndt/gft052.

20. Gomez-Sanchez, E. P., Ahmad, N., Romero, D. G., & Gomez-Sanchez, C. E. (2004). Origin of aldosterone in the rat heart. Endocrinology, 145 (11), 4796–4802. DOI: 10.1210/en.2004-0295.

21. Hamrah, M., Hamrah, M., Ishii, H., Suzuki, S., Hamrah, M., Hamrah, A., & Dahi, A. (2018). Left ventricular hypertrophy and proteinuria in patients with essential hypertension in Andkhoy, Afghanistan. Nagoya J. Med. Sci., 80 (2), 249–255. doi: 10.18999/nagjms.80.2.249.

22. Hernández-Socorro, C., Rodríguez-Esparragón, F., Celli, J., & López-Fernández, J. (2017). Sonographic evaluation of atherosclerosis burden in carotid arteries of ischemic stroke patients and its relation to paraoxonase 1 and 2, MTHFR and AT1R genetic variants. Journal of the Neurological Sciences, 378, 146–151. doi: 10.1016/j.jns.2017.05.010.

23. Hlubocká, Z., Jáchymová, M., Heller, S., Umnerová, V., Danzig, V., & Lánská, V. (2009). Association of the -344T/C aldosterone synthase gene variant with essential hypertension. Pysiological Research, 58 (6), 785–92.

24. Hwang, A. Y., Dietrich, E., Pepine, C. J., & Smith, S. M. (2017). Resistant Hypertension: Mechanisms and Treatment. Curr Hypertens Rep., 19 (7), 56. doi: 10.1007/s11906-017-0754-x.

25. Ji, L., Cai, X., Zhang, L., Fei, L., Wang, L., Su, J., … Zhang, Y. (2013). Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population. PLoS One, 8 (8), 1–6. doi: 10.1371/journal.pone.0072701.

26. Kupari, M., Hautanen, A., Lankinen, L., Koskinen, P., Virolainen, J., Nikkila, H., & White, P. (1998). Associations Between Human Aldosterone Synthase (CYP11B2) Gene Polymorphisms and Left Ventricular Size, Mass, and Function. Circulation, 97 (6), 569–75.

27. Lee, Y., Kim, J., Kim, K., Jang, H., Kim, J., Lee, J., Shin, I., … Kim, D. K. (2004). Aldosterone upregulates connective tissue growth factor gene expression via p38 MAPK pathway and mineralocorticoid receptor in ventricular myocytes. Journal of Korean Medical Science, 19 (6), 805–811. DOI:10.3346/jkms.2004.19.6.805.

28. Liu, D., Zhang, Y., Hu, B., Zhang, J., & Zhao, Q. (2015). Association of AT1R polymorphism with hypertension risk: An update meta-analysis based on 28,952 subjects. Journal of the Renin-Angiotensin-Aldosterone System, 16 (4), 898–909. doi: 10.1177/1470320315584096.

29. Lozinsky, S. (2016). The association of A1166C gene polymorphism of angiotensin receptors with the parameters of central pulse wave in normotensive persons and patients with hypertension. Folia Cardiologica, 11 (2), 180–185. DOI: 10.5603/FC.2016.0028.

30. MacKenzie, S. M., Davies, E., & Alvarez-Madrazo, S. (2017). Analysis of the Aldosterone Synthase (CYP11B2) and 11β-Hydroxylase (CYP11B1) Genes. Methods Mol. Biol., 1527, 139–150. doi: 10.1007/978-1-4939-6625-7_11.

31. Martínez-Quintana, E., Chirino, R., Nieto-Lago, V., Pérez-Jiménez, P., López-Ríos, L., & Rodríguez-González, F. (2014). Prognostic value of ACE I/D, AT1R A1166C, PAI-I 4G/5G and GPIIIa a1/a2 polymorphisms in myocardial infarction. Cardiology Journal, 21 (3), 229–237.

32. Neefs, J., van den Berg, N.W., Limpens, J., Berger, W. R., Boekholdt, S. M., Sanders, P., de Groot, J. R. (2017). Aldosterone Pathway Blockade to Prevent Atrial Fibrillation: A Systematic Review and Meta-Analysis. International Journal of Cardiology, 231, 155–161.

33. Park, J., Song, K., Jang, Y., & Kim Yoon, S. (2015). A polymorphism of the renin gene rs6682082 is associated with essential hypertension risk and blood pressure levels in Korean women. Yonsei Medical Journal, 56 (1), 227–34. doi: 10.3349/ymj.2015.56.1.227.

34. Rodilla, E., Pascual, J., Costa, J., Martin, J., Gonzalez, C., & Redon, J. (2013). Regression of left ventricular hypertrophy and microalbuminuria changes during antihypertensive treatment. Journal of Hypertension, 31 (8), 1683–1691. doi: 10.1097/HJH.0b013e328361461e.

35. Shenasa, M., & Shenasa, H. (2017). Hypertension, left ventricular hypertrophy, and sudden cardiac death. Int. J. Cardiol., 237, 60–63. doi: 10.1016/j.ijcard.2017.03.002.

36. Sookoian, S., Gianotti, T., & Pirola, C. (2009). Role of the C-344T aldosterone synthase gene variant in left ventricular mass and left ventricular structure-related phenotypes. Electrolyte Blood Press, 7 (2), 67–72. DOI:10.1136/hrt.2007.119545.

37. Starzhynska, O., Zhebel, V., & Blanar, O. (2012). Polymorphism Angiotensin II Type 1 Receptor Gene and Endothelial Dysfunction in Patients With Essential Hypertension and Congestive Heart Failure. Canadian Journal of Cardiology, 28 (5), S115. DOI: https://doi.org/10.1016/j.cjca.2012.07.088.

38. Stella, P., Bigatti, G., Tizzoni, L., Barlassina, C., Lanzani, C., Bianchi, G., Cusi, D. (2004). Association Between Aldosterone Synthase (CYP11B2) Polymorphism and Left Ventricular Mass in Human Essential Hypertension. Journal of the American College of Cardiology, 43 (2), 265–70. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14736447.

39. Tsai, C. T., Chang, S. N., Chang, S. H., Lee, J. K., Lin, L.Y., & Wu, C. K. (2014). Renin-angiotensin system gene polymorphisms predict the risk of stroke in patients with atrial fibrillation: a 10-year prospective follow-up study. Heart Rhythm, 11 (8), 1384–90. doi: 10.1016/j.hrthm.2014.04.014.

40. Vasan, R. S., Evans, J. C., Larson, M. G., Wilson, P. W., Meigs, J. B., Rifai, N. … Levy, D. (2004). Serum aldosterone and the incidence of hypertension in nonhypertensive persons. The New England Journal of Medicine, 351 (1), 33–41.

41. Wang, L., Zhou, J., Zhang, B., Wang, H., Li, M., Niu, Q., … Wen, S. (2015). Association of echocardiographic left ventricular structure and −344C/T aldosterone synthase gene variant: A meta-analysis. Journal of the Renin-AngiotensinAldosterone System, 16 (4), 858–871.

42. Xiaodan, F., Xiangyu, M., Li, Z., & Zhiyuan, S. (2015). Relationship between CYP11B2-344T>C polymorphsim and atrial fibrillation: A meta-analysis. Journal of the Renin-AngiotensinAldosterone System, 16 (1), 185–188.

43. Yamamoto, N., Yasue, H., Mizuno, Y., Yoshimura, M., Fujii, H., Nakayama, M., … Ogawa, H. (2002). Aldosterone is produced from ventricles in patients with essential hypertension. Hypertension, 39, 958–62. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/12019276.

44. Yang, Yu. (2015). The CYP11B2 −344C/T variant is associated with ischemic stroke risk: An updated meta-analysis. Journal of the Renin-AngiotensinAldosterone System, 16 (2), 382–388. https://doi.org/10.1177/1470320313492362.

45. Young, W. F. (2007). Adrenal causes of hypertension: pheochromocytoma and primary aldosteronism. Reviews in Endocrine and Metabolic Disorders, 8 (4), 309–320. DOI:10.1007/s11154-007-9055-z.

46. Zannad, F. Angiotensin-converting enzyme inhibitor and beta-blocker effects on the efficacy of eplerenone (EPHESUS). ESC Congress 2003; August 30-September 3, 2003; Vienna, Austria. Clinical Trial Update II: Heart Failure, Presentation #2458.

47. Zhang, H., Li, X., Zhou, L., Zhang, K., Zhang, Q., Li, J. … Qiu, C. (2017). A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension. Medicine (Baltimore), 96 (39), e8150. doi: 10.1097/MD.0000000000008150.

48. Zhang, J. A., Li, J. R., & Qiao, Y. J. (2015). Association of AGTR1 gene A1166C polymorphism with the risk of heart failure: a meta-analysis. Genetics and Molecular Research Journal, 14 (3), 9163–9170. doi: 10.4238/2015.August.7.26.
Published
2019-06-27
How to Cite
Lozinska, M. S., & Zhebel, V. M. (2019). Significance of aldosterone synthase gene (CYP11B2) polymorphism as a component of the renin-angiotensin-aldosterone system in the pathogenesis of myocardial hypertrophy in hypertension: literature review and own experience. Reports of Vinnytsia National Medical University, 23(2), 321-329. https://doi.org/https://doi.org/10.31393/reports-vnmedical-2019-23(2)-26