Russian Heart Failure Journal 2015year Effect of polymorphous gene variants in the renin-angiotensin-aldosterone system on phenotypic manifestations in patients with hypertrophic cardiomyopathy

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Effect of polymorphous gene variants in the renin-angiotensin-aldosterone system on phenotypic manifestations 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 Scientific Institution, "Institute of Genetics and Cytology of the Belarus National Academy of Sciences", Akademicheskaya 27, Minsk 220072
3 - State Scientific Institution, "United Institute of Informatics at the National Academy of Sciences of Belarus", Surganova 6, Minsk, Belarus

Keywords: HCMP, gene polymorphism, RAAS

DOI: 10.18087/rhfj.2015.2.2045

Background. Presently available studies of the relationship between polymorphism of modifier genes encoding RAAS components and phenotypic manifestations in patients with hypertrophic cardiomyopathy (HCMP) provide rather inconsistent results. Aim. To identify associations between polymorphism of genes encoding RAAS components (АСЕ, AGTR1, CYP11B2, and CMA1) with the clinical phenotype of disease considering sex, age and comorbidities of patients with HCMP. Materials and methods. Analysis of clinico-demographic and instrumental data was performed for 275 patients with HCMP (97 females and 178 males aged 17 to 70; median age 51 for females and 44 for males). PCR with subsequent restriction analysis was used for amplifying the polymorphous site of studied gene. Results. The monofactorial analysis showed that the presence of episodes of unstable paroxysmal ventricular tachycardia (UVT) was associated with ID polymorphism of the ACE gene and CC polymorphism of the AGTR1 gene (p=0.008, p=0.045, respectively). The presence of atrial fibrillation (AF) had a tendency to association with CC polymorphism of the AGTR1 gene (p=0.08). Angina of high FC II–III tended to associate with GA polymorphism of the СМА1 gene (p=0.06). The multifactorial analysis showed that carriers of ID heterozygous genotype in the ACE gene more frequently had paroxysmal or constant AF forms (OR, 2.06; 1.05–4.19, 95 % CI) than carriers of other genotypes. The presence of UVT episodes was more often associated with carriers of ID genotype in the ACE gene (OR, 2.44; 1.40–4.34, 95 % CI). High FC angina was more frequently observed in carriers of ID genotype in the ACE gene (OR, 2.17; 1.18–4.10, 95 % CI) and carriers of AA genotype in the СМА1 gene (OR, 2.09; 1.05–4.29, 95 % CI). Conclusion. ID genotype of the ACE gene polymorphism is the most unfavorable factor influencing the course of HCMP in the presence of high FC angina, development of life-threatening arrhythmias and AF with an account of age and presence of concurrent stage 2–3 arterial hypertension.
  1. Maron BJ, Gardin JM, Flack JM et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults: echocardiographic analisis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation. 1995 Aug 15;92 (4):785–9.
  2. Alcalai R, Seidman JG, Seidman CE. Genetic basis of hypertrophic cardiomyopathy from bench to the clinics. J Cardiovasc Electrophysiol. 2008 Jan;19 (1):104–10.
  3. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002 Mar 13;287 (10):1308–20.
  4. Maron BJ, Yeates L, Semsarian C. Clinical challeges of genotype positive (+) – phenotype negative (-) family members in hypertrophic cardiomyopathy. Am J Cardiol. 2011 Feb 15;107 (4):604–8.
  5. Maron BJ, Semsarian C. Emergence of gene mutation carriers and the expanding disease spectrum of hypertrophic cardiomyopathy. Eur Heart J. 2010 Jul;31 (13):1551–3.
  6. Marian AJ. Modifier genes for hypertrophic cardiomyopathy. Curr Opin Cardiol. 2002 May;17 (3):242–52.
  7. Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev. 2000 Mar;52 (1):11–34.
  8. Deinum J, van Gool JM, Koffard MJ et al. Angiotensin II type 2 receptors and cardiac hypertrophic in women with hypertrophic cardiomyopathy. Hypertension. 2001 Dec 1;38 (6):1278–81.
  9. Kumar R, Singh VP, Baker KM. The intracellular rennin-angiotensin system: implications in cardiovascular remodeling. Curr Opin Nephrol Hypertens. 2008 Mar;17 (2):168–73.
  10. Wang JG, Staessen JA. Genetic polymorphisms in the rennin-angiotensin system: relevance for susceptibility to cardiovascular disease. Eur j Pharmacol. 2000 Dec 27;410 (2-3):289–302.
  11. Kolder IC, Michels M, Christiaans I et al. The role of rennin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3‑related hypertrophic cardiomyopathy. Eur J Hum Genet. 2012 Oct;20 (10):1071–7.
  12. Elliott PM, Anastasakis A, Borger MA et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Forse for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology. Eur Heart J. 2014 Oct 14;35 (39):2733–79.
  13. Mathew CG. The isolation of high molecular weight eukaryotic DNA. Methods Mol Biol. 1985;2:31–4.
  14. Prasad A, Narayanan S, Husain S et al. Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE Inhibition. Circulation. 2000 Jul 4;102 (1):35–41.
  15. Venables WN, Ripley BD. Modern Applied Statistics with S. Fourth Edition. – Springer, 2002. – 495p.
  16. Marian AG, Yu QT, Workman R et al. Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. Lancet. 1993 Oct 30;342 (8879):1085–6.
  17. Tesson F, Dufour C, Moolman JC et al. The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation. J Mol Cell Cardiol. 1997 Feb;29 (2):831–8.
  18. Dellgren G, Eriksson MJ, Blange I et al. Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and regression in patients undergoing operation for aortic stenosis. Am J Cardiol. 1999 Oct 15;84 (8):909–13.
  19. Yamada Y, Ishihara S, Fujimura T et al. Lask of association of polymorphisms of the angiotensin converting enzyme and angiotensinogen genes with nonfamilial hypertrophic or dilated cardiomyopathy. Am J Hypertens. 1997 Aug;10 (8):921–8.
  20. Osterop AP, Kofflard MJ, Sandruijl LA et al. AT1 receptor A / C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy. Hypertension. 1998 Nov;32 (5):825–30.
  21. Lindpaintner K, Lee M, Larson MG et al. Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and ventricular mass. N Eng J Med. 1996 Apr 18;334 (16):1023–8.
  22. Ortlepp JR, Vosberg HP, Reith S et al. Genetic polymorphisms in the rennin-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 Mar;87 (3):270–5.
  23. McLeod CJ, Bos JM, Theis JL et al. Histologic characterization of hypertrophic cardiomyopathy with and without myofilament mutations. Am Heart J. 2009 Nov;158 (5):799–805.
  24. Pfeufer A, Osterziel KJ, Urata H et al. Angiotensin-converting enzyme and heart chymase gene polymorphisms in hypertrophic cardiomyopathy. Am J Cardiol. 1996 Aug 1;78 (3):362–4.
Komissarova S. M., Niyazova S. S., Chakova N. N. et al. Effect of polymorphous gene variants in the renin-angiotensin-aldosterone system on phenotypic manifestations in patients with hypertrophic cardiomyopathy. Russian Heart Failure Journal. 2015;16 (2):100–105

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