2015


To access this material please log in or register

Register Authorize
2015/№3

Effect of polymorphic gene variants in the renin-angiotensin-aldosterone system on parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy

Komissarova S. M.1, Niyazova S. S.2, Chakova N. N.2, Krasko O. V.3
1 – State Institution, Republican Science and Practice Center “Cardiology”, R. Luxemburg 110, Minsk 220036, Belarus
2 – State Science Institution, “Institute of Genetics and Cytology of Belarus National Academy of Sciences”, Akademicheskaya 27, Minsk 220072, Belarus
3 – State Science Institution, “United Institute of Informatics Issues of the Belarus National Academy of Sciences”, Surganova 6, Minsk 220012, Belarus

Keywords: hypertrophic cardiomyopathy, renin-angiotensin-aldosterone system, polymorphism

DOI: 10.18087/rhfj.2015.3.2055

Background. A major sign of hypertrophic cardiomyopathy (HCMP) is LV myocardial hypertrophy. The article discusses the role of gene polymorphism in RAAS components in progression of LV myocardial hypertrophy. Results of studies focused on the relationship between gene polymorphism in RAAS components and signs of LV myocardial hypertrophy in patients with HCMP are inconsistent. This inconsistency is partially due to different gender and age composition of study groups. Aim. To establish associations between polymorphism of genes encoding RAAS components (АСЕ, AGTR1, CYP11B2, and CMA1) and EchoCG signs of LV myocardial hypertrophy considering gender, age and concomitant diseases of patients with HCMP. Materials and methods. Clinico-demographic and EchoCG data were analyzed for 275 patients with HCMP (97 females and 178 males aged 17 to 70, median age 51 for females and 44 for males) who were examined and treated at the Russian Science and Practice Center “Cardiology”. All parameters were evaluated during enrollment. Polymorphic sites of study genes were amplified using PCR followed by restriction analysis. Results. Monofactorial analysis showed that higher values of left ventricular myocardial mass (LVMM) and myocardial mass index (MMI) were associated with the ACE II gene polymorphism (p=0.07, p=0.04, respectively). Similar associations with LVMM and MMI were observed for the CMA1 AA gene polymorphism (p=0.03, p=0.04, respectively). Multifactorial analysis showed that LVMM values were significantly higher in carriers of the genotype II of ACE gene (mean percentage of increase, 10.8; 1.9–20.1; 95% CI) compared to the other genotypes. Values of MMI were significantly higher in carriers of the genotype II of the ACE gene (mean percentage of increase, 9.1; 1.0–17.6, 95% CI) and carriers of the AA genotype of CMA gene (mean percentage of increase, 7.3; 0.0–14.8; 95% CI) compared to the other genotypes. Gender and concomitant stage 2–3 AH influenced the studied EchoCG parameters. Conclusion. Genotype II of the ACE gene polymorphism and genotype AA of the CMA gene are the most unfavorable factors influencing parameters of LV myocardial hypertrophy in patients with HCMP.
  1. Maron B. J., Gardin J. M., Flack J. M., Gidding S. S., Kurosaki T. T., Bild D. E. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation. 1995;92 (4):785–789.
  2. Maron B. J. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002;287 (10):1308–1320.
  3. Maron B. J., Yeates L., Semsarian C. Clinical challenges of genotype positive (+) – phenotype negative (-) family members in hypertrophic cardiomyopathy. Am. J. Cardiol. 2011;107 (4):604–608.
  4. Marian A. J. Modifier genes for hypertrophic cardiomyopathy. Curr. Opin. Cardiol. 2002;17 (3):242–252.
  5. Wei C.‑C., Meng Q. C., Palmer R., Hageman G. R., Durand J., Bradley W. E., et al. Evidence for Angiotensin-Converting Enzyme– and Chymase-Mediated Angiotensin II Formation in the Interstitial Fluid Space of the Dog Heart In Vivo. Circulation. 1999;99 (19):2583–2589.
  6. Kumar R., Singh V. P., Baker K. M. The intracellular renin-angiotensin system: implications in cardiovascular remodeling. Curr. Opin. Nephrol. Hypertens. 2008;17 (2):168–173.
  7. Yamada Y., Ichihara S., Fujimura T., Yokota M. Lack of association of polymorphisms of the angiotensin converting enzyme and angiotensinogen genes with nonfamilial hypertrophic or dilated cardiomyopathy. Am. J. Hypertens. 1997;10 (8):921–928.
  8. Authors / Task Force members, Elliott P. M., Anastasakis A., Borger M. A., Borggrefe M., Cecchi F., et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur. Heart J. 2014;35 (39):2733–2779.
  9. Mathew C. G. The isolation of high molecular weight eukaryotic DNA. Methods Mol. Biol. 1985;231–34.
  10. Chen L.‑Y., Li P., He Q., Jiang L.‑Q., Cui C.‑J., Xu L., et al. Transgenic study of the function of chymase in heart remodeling. J. Hypertens. 2002;20 (10):2047–2055.
  11. Perkins M. J., Van Driest S. L., Ellsworth E. G., Will M. L., Gersh B. J., Ommen S. R., et al. Gene-specific modifying effects of pro-LVH polymorphisms involving the renin-angiotensin-aldosterone system among 389 unrelated patients with hypertrophic cardiomyopathy. Eur. Heart J. 2005;26 (22):2457–2462.
  12. Ortlepp J. R., Vosberg H. P., Reith S., Ohme F., Mahon N. G., Schröder D., et al. Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Heart. 2002;87 (3):270–275.
  13. López-Haldón J., García-Lozano J. R., Martínez Martínez A., Núñez-Roldán A., Burgos Cornejo J. [The effect of polymorphisms of the angiotensin-converting enzyme and angiotensinogen genes on the phenotypic expression of Spanish patients with hypertrophic cardiomyopathy]. Med Clin (Barc). 1999;113 (5):161–163.
  14. Kolder I. C. R. M., Michels M., Christiaans I., Cate F. J. Ten, Majoor-Krakauer D., Danser A. H. J., et al. The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3‑related hypertrophic cardiomyopathy. Eur. J. Hum. Genet. 2012;20 (10):1071–1077.
  15. Wang X., Zhu H., Dong Y., Treiber F. A., Snieder H. Effects of angiotensinogen and angiotensin II type I receptor genes on blood pressure and left ventricular mass trajectories in multiethnic youth. Twin Res Hum Genet. 2006;9 (3):393–402.
  16. Osterop A. P., Kofflard M. J., Sandkuijl L. A., Cate F. J. ten, Krams R., Schalekamp M. A., et al. AT1 receptor A / C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy. Hypertension. 1998;32 (5):825–830.
  17. Смирнова М. Д. Генетические аспекты гипертрофии миокарда при гипертрофической кардиомиопатии и артериальной гипертонии. Терапевтический архив.;80 (1):77–84.
  18. Kupari M., Hautanen A., Lankinen L., Koskinen P., Virolainen J., Nikkila H., et al. Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Circulation. 1998;97 (6):569–575.
  19. Pfeufer A., Osterziel K. J., Urata H., Borck G., Schuster H., Wienker T., et al. Angiotensin-converting enzyme and heart chymase gene polymorphisms in hypertrophic cardiomyopathy. Am. J. Cardiol. 1996;78 (3):362–364.
  20. Weinberg E. O., Thienelt C. D., Katz S. E., Bartunek J., Tajima M., Rohrbach S., et al. Gender differences in molecular remodeling in pressure overload hypertrophy. J. Am. Coll. Cardiol. 1999;34 (1):264–273.
  21. Schunkert H., Hense H. W., Muscholl M., Luchner A., Kürzinger S., Danser A. H., et al. Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass. Heart. 1997;77 (1):24–31.
Komissarova S. M., Niyazova S. S., Chakova N. N., Krasko O. V. Effect of polymorphic gene variants in the renin-angiotensin-aldosterone system on parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. Russian Heart Failure Journal. 2015;16 (3):161–166

To access this material please log in or register

Register Authorize
Ru En