Gene polymorphism of aldosterone synthetase (CYP11B2) variants and main cardiovascular risk factors

Authors

  • L. Ye. Lobach P.L. Shupyk National Medical Academy of Postgraduate Education, Kiev,
  • V. Ye. Dosenko Bogomolets Institute of Physiology, Kiev,
  • M. M. Dolzhenko P.L. Shupyk National Medical Academy of Postgraduate Education, Kiev,

DOI:

https://doi.org/10.14739/2310-1210.2016.6.85482

Keywords:

Genetic Polymorphism, CYP11B2–344C/T, Myocardial Ischemia, Postinfarction Cardiosclerosis, Infarction, Risk Factors

Abstract

Background. Purpose of the work – to investigate the possible relationship of the cardiovascular risk main factors with certain polymorphism of aldosterone synthase gene (CYP11B2).

Materials and methods. Аt the Cardiology Department of PL Shupyk NMAPE general clinical examination of 378 patients was held. Patients were divided into four groups: 100 patients with postinfarction cardiosclerosis, 78 patients with CAD without myocardial infarction in history, 100 high cardiovascular risk patients (with diabetes, hypertension or dyslipidemia) and 100 healthy patients (absence of cardiovascular disease was confirmed by medical history, ECG, blood pressure measurement and stress-ECG).

Genetic testing was performed by polymerase chain reaction in real time at the Institute of Physiology named after O. O. Bogomolets.

Exclusion criteria were hemodynamically significant valvular heart disease, chronic obstructive pulmonary disease, permanent or temporary heart pacing, acute heart failure and implanted cardioverter-defibrillator, permanent form of atrial fibrillation.

Statistical analysis of the results was performed using Microsoft Excel, the statistical program SPSS (version 13US).

Results. When analyzing the average levels of low density lipoprotein (LDL) cholesterol statistically significant difference between the group of patients with postinfarction cardiosclerosis and the group of high-risk patients (2.93±1.2 mmol/L vs 3.4±1.2 mmol/L, p=0.0075) was demonstrated, indicating a better cholesterol control in the group of patients with postinfarction cardiosclerosis, despite the fact that the average cholesterol level did not reach the target.

The highest average levels of triglycerides (TG) were observed in patients with postinfarction cardiosclerosis – 1.56±0.725 mmol/L, intermediate – in patients with stable coronary artery disease – 1.39±0.795 mmol/L, and the lowest – in high cardiovascular risk patients – 1.04±0.565 mmol/L, with significant differences between all groups. The level of total cholesterol in patients with postinfarction cardiosclerosis was significantly higher in the subgroup of patients with homozygous recessive variant CC (5.8±1.08 mmol/L), compared with heterozygotes TC (4.87±1.3 mmol/L, p=0.024 ) and had no statistical significance when compared with the dominant TT homozygotes (5.06±1.45 mmol). Higher levels of total cholesterol (5.76±1.5 mmol/L) in TT homozygotes compared with TC (4.92±1.27 mmol/L, p=0.027) and CC (4.74±1.23 mmol/L, p=0.022) were found. In the group of patients with postinfarction cardiosclerosis, LDL cholesterol in the subgroup homozygous recessive variant CC was higher (3.43±0.87 mmol/L) (not significant) compared with a TT variant (3.02±1.3 mmol/L) and compared with heterozygotes TC (2.78±1.2 mmol/L, p=0.08). The level of TG in patients with stable coronary heart disease was the lowest in dominant homozygotes TT (1.13±0.56 mmol/L) compared with CT heterozygotes (1.54±0.97 mmol/L, p=0.08) and CC homozygotes (1.36±0.58 mmol/L, p=0.2).

Conclusions.

1. Group of high cardiovascular risk patients requires special attention in the prevention of cardiovascular diseases, because this group showed the worst control of cardiovascular risk factors (level of total cholesterol, LDL cholesterol, glucose, SBP) in the absence of appropriate treatment.

2. Ingroup of patients with stable coronary artery disease and postinfarction cardiosclerosis the link CC variant gene polymorphism of aldosterone synthase CYP11B2-344C/T with higher levels of total cholesterol, LDL cholesterol was established, which increases the cardio-vascular risk in this group.

3. CC polymorphism of aldosterone synthase gene CYP11B2-344C/T was associated with higher levels of SBP in patients with stable coronary artery disease and postinfarction cardiosclerosis, which increases the cardiovascular risk such as the development of hypertension.

References

Kowalski, J., Barylski, M., Banach, M., Grycewicz, J., Irzmański, R., & Pawlicki, L. (2006). Neutrophil superoxide anion generation during atorvastatin and fluvastatin therapy used in coronary heart disease primary prevention. J Cardiovasc Pharmacol, 48, 143–147. doi: 10.1097/01.fjc.0000246150.52382.07.

Ebrahim, S., & Smith, G. D. (1997). Systematic review of randomised controlled trials of multiple risk factor interventions for preventing coronary heart disease. BMJ, 314, 1666–1674. doi: http://dx.doi.org/10.1136/bmj.314.7095.1666.

Kraus, W. E. (2000). Genetic approaches for the investigation of genes associated with coronary heart disease. Am Heart J, 140, 27–35. doi: 10.1067/mhj.2000.109380.•

Levy, D, DeStefano, A. L., Larson, M. G., O'Donnell, C. J., Lifton, R. P., Gavras, H., et al. (2004). Evidence for a blood pressure gene on chromosome 17: Genome scan results for longitudinal blood pressure phenotypes in subjects from the Framingham Heart Study. Hypertension, 36, 477–483.

O’Donnell, C. J. (2004). Family history, subclinical atherosclerosis, and coronary heart disease risk barriers and opportunities for the use of family history information in risk prediction and prevention. Circulation, 110, 2074–2076. doi: http://dx.doi.org/10.1161/01.CIR.0000145539.77021.AC.

Hanatani, A., Yoshiyama, M., Kim, S., Omura, T., Toda, I., Akioka, K., et al. (1995). Inhibition byangiotensin II type I receptor antagonist of cardiac phenotypic modulation after myocardial infarction. J Mol Cell Cardiol, 27, 1905–1914.

Urata, H., Boehm, K. D., Philip, A., Kinoshita, A., Gabrovsek, J., Bumpus, F. M., & Husain, A. (1993). Cellular localization and regionaldistribution of an angiotensin II forming chymase in the heart. J Clin Invest, 91, 1269–128.

Brilla, C. G., Pick, R., Tan, L. B., Janicki, J. S., & Weber, K. T. (1990). Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res, 67, 1355–1364. doi: http://dx.doi.org/10.1161/01.RES.67.6.1355.

Tsai, C. T., Lai, L. P., Lin, J. L., Chiang, F. T., Hwang, J. J., Ritchie, M. D., et al. (2004). Reninangiotensinsystem gene polymorphisms and atrial fibrillation. Circulatio, 109, 1640–1646. doi: http://dx.doi.org/10.1161/01.CIR.0000124487.36586.26.

Weber, K. T., Brilla, C. G., & Janicki, J. S. (1993). Myocardial fibrosis:functional significance and regulatory factors. Cardiovasc Res, 27, 341–348.

Williams, G. H., Moore, T. J., & Hollenberg, N. K. (1991). Dysregulation of aldosterone secretion and its relationship to the pathogenesis ofessential hypertension. Endocrinol Metab Clin North America, 20, 423–447.

Refaat, S., El-Ghaffar, N. A., El-Rahman Negm, H. A., & Yousri, T. (2008). The role of aldosterone in myocardial dysfunction of Egyptianpatients with essential hypertension. Arch Med Sci, 4, 161–166.

Cohn, J. N., & Colucci, W. (2006). Cardiovascular effects of aldosterone and post-acute myocardial infarction pathophysiology. AmCardiol, 97, 4–12.

Donderski, R., Grajewska, M., & Manitius, J. (2006). Aldosteron i jego znaczenie w uszkodzeniu układu sercowo-naczyniowego u osób z przewlekłą chorobą nerek. Kardiol Pol, 64, 423–42.

Sutton, M. G., & Sharpe, N. (2000). Left ventricular remodeling aftermyocardial infarction pathophysiology and therapy. Circulation, 101, 2981–2988. doi: http://dx.doi.org/10.1161/01.CIR.101.25.2981.

Ouvrard-Pascaud, A., Sainte-Marie, Y., Bénitah, J. P., Perrier, R.,Soukaseum, C., Cat, A. N., et al. (2005). Conditional mineralocorticoidreceptor expression in the heart leads to life-threatening arrhythmias. Circulation, 111, 3025–3033. doi: http://dx.doi.org/10.1161/CIRCULATIONAHA.104.503706.

Marumo, T., Uchimura, H., Hayashi, M., Hishikawa, K., & Fujita, T. (2006). Aldosterone impairs bone marrow-derived progenitor cell formation. Hypertension, 48, 490–496. doi: http://dx.doi.org/10.1161/01.HYP.0000235681.25685.cf.

Qin, W., Rudolph, A. E., Bond, B. R., Rocha, R., Blomme, E. A., Goellner, J. J., et al. (2003). Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res, 93, 69–76. doi: http://dx.doi.org/10.1161/01.RES.0000080521.15238.E5.

Biondi-Zoccai, G. G., Abbate, A., & Baldi, A. (2003). Potential antiapoptotic activity of aldosterone antagonists in postinfarction remodeling. Circulation, 108, 26.

Kupari, M., Hautanen, A., Lankinen, I., Koskinen, P., Virolainen, J., Nikkila, H., & White, P.C. (1998). Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation, 97, 569–575. doi: http://dx.doi.org/10.1161/01.CIR.97.6.569.

White, P. C., & Slutsker, L. (1995). Haplotype analysis of CYP11B2. Endocr Res, 21, 437–442.

Davies, E., Holloway, C. D., Ingram, M. C., Inglis, G. C., Friel, E. C., Morrison, C., et al. (1999). Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension, 33, 703–707. doi: 10.1161/01.HYP.33.2.703. •

Lala, D. S., Rice, D. A., & Parker, K. L. (1992). Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I. Mol. Endocrinol, 6, 1249–1258.

Tamaki, S., Iwai, N., Tsujita, Y., & Kinoshita, M. (1999). Genetic polymorphism of CYP11B2 gene and hypertension in Japanese. Hypertension, 33, 266–270. doi: http://dx.doi.org/10.1161/01.HYP.33.1.266.

Stella, P., Bigatti, G., & Tizzoni, L. (2004). Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension. J Am CollCardiol, 43, 265–270. doi:10.1016/j.jacc.2003.08.034.

Isaji, M., Mune, T., & Takada, N. (2005). Correlation between left ventricular mass and urinary sodium excretion in specific genotypes of CYP11B2. J Hypertens, 23, 1149–1157. doi: 10.1097/01.hjh.0000170377.00591.7e.

Wang, L., Zhou, J., Zhang, B., Wang, H., Li, M., Niu, Q., et al. (2014). Association of echocardiographic left ventricular structure and −344C/T aldosterone synthase gene variant: A meta-analysis, Journal of Renin-Angiotensin-Aldosterone System, 1–14. doi: 10.1177/1470320314535459.

Takeuchi, F., Yamamoto, K., & Katsuya, T. (2012). Reevaluation of the association of seven candidate genes with blood pressure and hypertension: A replication study and meta-analysis with a larger sample size. Hypertens Res, 35, 825–831. doi: 10.1038/hr.2012.43.

Saidi, S., Touhami, M., & Wassim, A. (2010). Aldosterone synthase gene (CYP11B2) promoter polymorphism as a risk factor for ischaemic stroke in Tunisian Arabs. Journal of Renin-Angiotensin-Aldosterone System, 11(3), 180–6. doi: 10.1177/1470320309360816.

How to Cite

1.
Lobach LY, Dosenko VY, Dolzhenko MM. Gene polymorphism of aldosterone synthetase (CYP11B2) variants and main cardiovascular risk factors. Zaporozhye Medical Journal [Internet]. 2016Dec.8 [cited 2024Nov.23];18(6). Available from: http://zmj.zsmu.edu.ua/article/view/85482

Issue

Section

Original research