Clinical significance of the T(-344)C polymorphism of the aldosterone synthase gene (CYP11B2) in the prognosis of cardiorenal syndrome in diabetes mellitus
https://doi.org/10.51523/2708-6011.2022-19-4-07
Abstract
Objective. To evaluate the role of the T(-344)C polymorphism of CYP11B2 gene in the development of cardiorenal syndrome (CRS) in diabetes mellitus (DM).
Materials and methods. 270 patients with type 1 and type 2 diabetes aged over 25 years were examined. All patients underwent molecular genetic analysis using deoxyribonucleic acid isolated from whole venous blood.
Results. The TT genotype was associated with the risk of developing CRS manifestations such as left ventricular hypertrophy (odds ratio (OR) 2.64; 95% CI (0.93–4.19), chronic heart failure (OR 4.26; 95% CI (2.26 - 8.06), subclinical atherosclerosis (OR 4.04; 95% CI (1.89 - 8.58), chronic kidney disease (CKD) (OR 10.77; 95% CI (3.56 - 32.61), and the CT genotype (OR 3.28; 95% CI (1.02 – 10.59) with CKD risk..
Conclusion. There are pathogenetic associations between renin-angiotensin-aldosterone system, cardiovascular complications and a decrease of renal function. Further research is needed for a deep understanding of the complex pathogenetic mechanisms of the development and progression of cardiovascular and renal pathology.
Supporting agencies: This study was supported by the Belarusian Foundation for Basic Research (BFBR) (research project No. М17РМ-113) and Russian Foundation for Basic Research (RFBR) (research project No.17-54-04080)
About the Authors
V. N. Vasilkova
Gomel State Medical University
Belarus
Belarus
Volha N. Vasilkova, Candidate of Medical Sciences,
Associate Professor of the Department of Internal Diseases №1 with a course of Endocrinology
Gomel
I. Yu. Pchelin
St. Petersburg State University
Russian Federation
Russian Federation
Ivan Yu. Pchelin, Candidate of Medical Sciences, Associate Professor performing clinical work at the Department of Faculty Therapy
St. Petersburg
Ya. A. Borovets
Gomel State Medical University
Belarus
Belarus
Yana A. Borovets, Assistant of the Department of Internal Diseases №1 with a course of Endocrinology
Gomel
I. A. Vasukhina
Republican Research Center for Radiation Medicine and Human Ecology
Belarus
Belarus
Irina A. Vasukhina, Endocrinologist
Gomel
T. V. Mokhort
Belarusian State Medical University
Belarus
Belarus
Tatsiana V. Mokhort, Doctor of Medical Sciences,
Professor, Head of the Department of Endocrinology
Minsk
References
1. Htay T, Soe K, Lopez-Perez A, Doan AH, Romagosa MA, Aung K. Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes. Curr Cardiol Rep. 2019;21(6):45. DOI: https://doi.org/10.1007/s11886-019-1133-9
2. Poznyak AV, Bharadwaj D, Prasad G, Grechko AV, Sazonova MA, Orekhov AN. Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD. Int J Mol Sci. 2021;22;22(13):6702. DOI: https://doi.org/10.3390/ijms22136702
3. Böckmann I, Lischka J, Richter B, Deppe J, Rahn A, Fischer DC, Heineke J, Haffner D, Leifheit-Nestler M. FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis. Int J Mol Sci. 2019;18;20(18):4634. DOI: https://doi.org/10.3390/ijms20184634
4. Pattacini L, Casali B, Boiardi L, et al. Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF- kappaB pathway. Rheumatology (Oxford). 2007 Aug;46(8):1252-1257. DOI: https://doi.org/10.1093/rheumatology/kem092
5. Seredyuk V. Role of aldosterone, mitogenic growth factors, apoptosis inducers and pulmonary arterial hypertension in the formation and progression of chronic pulmonary heart disease. Pharm Innovat J. 2013;2(5):36-40.
6. Naccarelli GV, Filippone EJ, Foy A. Do Mineralocorticoid Receptor Antagonists Suppress Atrial Fibrillation/Flutter? J Am Coll Cardiol. 2021;78(2):153-155. DOI: https://doi.org/10.1016/j.jacc.2021.04.080
7. Lu WH, Bayike M, Liu JW, Wang S, et al. Association between aldosterone synthase (CYP11B2) -344C/T polymorphism and atrial fibrillation among Han and Kazak residents of the Xinjiang region. Int J Clin Exp Med. 2015;8(4):5513-5519.
8. Abdel Ghafar MT. Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population. Clin Exp Hypertens. 2019;41(8):779-786. DOI: https://doi.org/10.1080/10641963.2018.1557679
9. Elgazzaz M, Lazartigues E. Epigenetic modifications of the renin-angiotensin system in cardiometabolic diseases. Clin Sci (Lond). 2021;135(1):127-142. DOI: https://doi.org/10.1042/CS20201287
10. Abdel Ghafar MT. Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population. Clin Exp Hypertens. 2019;41(8):779-786. DOI: https://doi.org/10.1080/10641963.2018.1557679
11. Nishiyama A, Kobori H. Independent regulation of reninangiotensin-aldosterone system in the kidney. Clin Exp Nephrol. 2018;22(6):1231-1239. DOI: https://doi.org/10.1007/s10157-018-1567-1
12. Shrestha A, Che RC, Zhang AH. Role of Aldosterone in Renal Fibrosis. Adv Exp Med Biol. 2019;1165:325-346. DOI: https://doi.org/10.1007/978-981-13-8871-2_15
13. Svenningsen P, Hinrichs GR, Zachar R, Ydegaard R, Jensen BL. Physiology and pathophysiology of the plasminogen system in the kidney. Pflugers Arch. 2017 Nov;469(11):1415- 1423. DOI: https://doi.org/10.1007/s00424-017-2014-y
14. Monticone S, D’Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41-50. DOI: https://doi.org/10.1016/S2213-8587(17)30319-4
15. Byrd JB, Auchus RJ, White PC. Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a Large, Multiethnic Population-Based Study. J Investig Med. 2015;63(7):862-866. DOI: https://doi.org/10.1097/JIM.0000000000000220
16. Yin C, Gu W, Gao Y, Li Z, Chen X, Li Z, Wen S. Association of the -344T/C polymorphism in aldosterone synthase gene promoter with left ventricular structure in Chinese Han: A meta-analysis. Clin Exp Hypertens. 2017;39(6):562-569. DOI: https://doi.org/10.1080/10641963.2017.1291660
17. Dai B, David V, Martin A, et al. A comparative transcriptome analysis identifying FGF23 regulated genes in the kidney of a mouse CKD model. PLoS One. 2012;7:e44161. DOI: https://doi.org/10.1371/journal.pone.0044161
18. Prud’homme GJ, Kurt M, Wang Q. Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations. Front Aging. 2022;12(3):931331. DOI: https://doi.org/10.3389/fragi.2022.93133
19. Imazu M, Takahama H, Asanuma H, et al. Pathophysiological impact of serum fibroblast growth factor 23 in patients with non-ischemic cardiac disease and early chronic kidney disease. Am J Phys. 2014;307:H1504-1511. DOI: https://doi.org/10.1152/ajpheart.00331.2014
20. Zhang B, Umbach AT, Chen H, et al. Up-regulation of FGF23 release by aldosterone. Biochem Biophy Res Commun. 2016;470:384-390. DOI: https://doi.org/10.1016/j.bbrc.2016.01.034
21. Syed SB, Qureshi MA. Association of aldosterone and cortisol with cardiovascular risk factors in prehypertension stage. Int J Hypertens. 2012;2012:906327. DOI: https://doi.org/10.1155/2012/906327
22. Sjöberg B, Anderstam B, Suliman M, Alvestrand A. Plasma reduced homocysteine and other aminothiol concentrations in patients with CKD. Am J Kidney Dis. 2006;47(1):60-71. DOI: https://doi.org/10.1053/j.ajkd.2005.09.032
23. Karolczak K, Kubalczyk P, Glowacki R, Pietruszynski R, Watala C. Aldosterone modulates blood homocysteine and cholesterol in coronary artery disease patients - a possible impact on atherothrombosis? Physiol Res. 2018;4;67(2):197-207. DOI: https://doi.org/10.33549/physiolres.933668
Review
For citations:
Vasilkova V.N., Pchelin I.Yu., Borovets Ya.A., Vasukhina I.A., Mokhort T.V. Clinical significance of the T(-344)C polymorphism of the aldosterone synthase gene (CYP11B2) in the prognosis of cardiorenal syndrome in diabetes mellitus. Health and Ecology Issues. 2022;19(4):48-55. (In Russ.) https://doi.org/10.51523/2708-6011.2022-19-4-07
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