POLYMORPHIC VARIANTS OF GENES CODING SYMPATHOADRENAL SYSTEM INFLUENCE ON PHENOTYPE OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
https://doi.org/10.15829/1560-4071-2015-6-75-80
Abstract
Aim. To reveal the associations of polymorphic genes variants coding the proteins of sympathoadrenal system (ADRB1 and ADRB2) with clinical phenotype of the disease including age and gender of patients with HCMP.
Material and methods. The analysis of clinical-demographic and instrumental data of 275 patients with the diagnosis of HCMP (97 women and 178 men, age 17 to 70 y.o., median age 51 y. and 44 y., resp.) was done. All parameters were assessed at the moment of the patients inclusion. Amplification of polymorphic area of the gene was done by PCR method with consequent restriction analysis.
Results. Monofactor analysis revealed that atrial fibrillation (AF) is associated with polymorphism of Arg389Gly gene АDRB1 (p=0,028). Heart failure of the higher FC II-III showed tendency to association with polymorphism Arg389Gly gene АDRB1 (p=0,060). Multifactorial analysis showed that the presence of nonsustained ventricular tachycardia episodes (NVT) more often associated with the patients — carriers of heterozygous GC gene АDRB2 (polymorphism Gln27Glu) (OR 1,76; 1,023,06; 95% CI). AF was more rare in the carriers of heterozygous genotype of GC gene АDRB1 (polymorphism Arg389Gly) (OR 0,39 (0,17-0,82; 95% CI) comparing to the normal genotypes. Heart failure of higher FC II-III more often was found in patients — carriers of GC gene АDRB1 (polymorphism Gln27Glu) (OR 4,31; 1,0829,03; 95% CI).
Conclusion. Genotype GC of polymorphism gene АDRB2 (polymorphism Gln27Glu) is the most adverse factor that influence such clinical presentations of HCMP as the higher functional class of heart failure and development of life threatening arrhythmias.
About the Authors
S. M. Komissarova
Republic Scinetific-Practice Center “Cardiology”, Minsk
Belarus
Belarus
S. S. Nyazova
Institute of Genetics and Cytology of NSA Belarus, Minsk
Belarus
Belarus
N. N. Chakova
Institute of Genetics and Cytology of NSA Belarus, Minsk
Belarus
Belarus
O. V. Krasko
United Institute of Informatics Problems of NAS Belarus, Minsk
Belarus
Belarus
References
1. Elliott P, Anastasakis A, Borger MA, et al. Guidelines for the 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; 10:1093. 2. Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopathy after 20 years: clinical perspectives. J Amer. Coll. Cardiol. 2012; 60 (8): 705-15.
2. Marian AJ. Genetic determinants of cardiac hypertrophic. Curr Opin Cardiol. 2008; 23: 199-205.
3. Brodde OE. Beta-1 and beta-2 adrenoreceptor polymorphisms: functional impotance, impact on cardiovascular disease and drug responses . Pharmacol Ther. 2008; 117: 1-29.
4. Brodde OE. Beta-1 and beta-2 adrenoreceptor polymorphisms and cardiovascular diseases. Fundam. Clin. Pharmacol. 2008; 22: 107-25.
5. Bruck H, Leineweber K, Temme T, et al. The Arg389Glu beta1-adrenoreceptor polymorphism and catecholamine effects on plasma-renin activity. J Am Coll Cardiol. 2005; 46 (11): 2111-5.
6. Shioji K, Kokubo Y, Mannami T, et al. Association between hypertension and the alphaadducin, beta1-adrenoreceptor, and G-protein beta 3 subunit genes in the Japanese population; the Suita study. Hypertens Res. 2004; 27(1): 31-7.
7. Leineweber K, Rohe P, Beilfuss A, et al. G-protein coupled receptor kinase activity in human heart failure: effects of beta-adrenoceptor blockade. Cardiovascular Res. 2005; 66: 512–9.
8. Brodde OE, Bruck H, Leineweber K. Cardiac adrenoceptoors: physiological and pathophisiological relevance. J Pharmacol Sci. 2006; 100: 323-37.
9. Olivotto I, Maron M, Adabag A, et al. Gender-Related Differences in the clinical Presentation and outcome of Hypertrophic Cardiomyopathy. J Am Coll Card. 2005; 46 (3): 480–7.
10. Mathew CС. The isolation of high molecular weight eukaryotic DNA. Methods Mol. Biol. 1985; 2: 31-4.
11. Biolo A, Rosa AS, Mazzotti NG, et al. The role of adrenergic receptor polymorphisms in heart failure. Brazilian Journal of Medical and Biological Research. 2006; 39: 1281-90.
12. Iwai C, Akita H, Shiga N, et al. Suppressive effect of the Gly389 allele of the beta1adrenergic receptor gene on the occurrence of ventricular tachycardia in dilated cardiomyopathy. Circ J. 2002; 66: 723–728.
13. Iwai C., Akita H., Kanazawa K, et al. Arg389Gly polymorphism of the human β1-adrenergic receptor in patients with nonfatal myocardial infarction. Am Heart J. 2003; 146: 106–9.
14. Covolo L, Gelatti U, Metra M. Role of β1and β2-adrenoreceptor polymorphisms in heart failure: a case-control study. Eur. Heart J. 2004; 25: 1534-41.
15. Nonen S, Okamoto H, Akino M, et al. No positive association between adrenergic receptor variants of alpha 2cDel389 and the risk for heart failure in the Japanese population. Br J Clin Pharmacol. 2005; 60(4): 414-7.
16. De Groote P, Lamblin N, Helbecque N, et al. The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure. Eur J Heart Fail.2005; 7(6): 966-73.
17. Herrmann SM, Nicaud V, Tired L, et al. Polymorphisms of the ADRB2 gene and essential hypertension: the ESTIM and PEGASE studies J. Hypertens.2002; 20: 229-35. 1
18. Castellano M, Rossi F, Giacche M, et al. Β2-adrenergic receptor gene polymorphism, age, and cardiovascular phenotype. Hypertension 2003; 41: 361-7.
19. Bray M, Krushkal J, Ferrell R, et al. Positional genomic analysis identifies the β2-adrenergic receptor gene as susceptibilility locus for human hypertension. Circulation. 2000; 101: 2877-882.
20. Smirnova MD, Fofanova TV, Khasanova ZB, et al. Clinical manifestation and severity of LV hypertrophy depending on ADRB2 gene polymorphism in subjects with hypertrophic cardiomyopathy and hypertensive heart. Cardiologichesky vestnik. 2009; 1: 7–11. Russian. (Смирнова M.Д., Фофанова Т.В., Хасанова З.Б. и др. Клиническая картина и выраженность гипертрофии левого желудочка в зависимости от полиморфизма гена ADRB2 у больных с гипертрофической кардиомиопатией и гипертоническим сердцем. Кардиологический вестник. 2009; 1: 7-11).
Review
For citations:
Komissarova S.M., Nyazova S.S., Chakova N.N., Krasko O.V. POLYMORPHIC VARIANTS OF GENES CODING SYMPATHOADRENAL SYSTEM INFLUENCE ON PHENOTYPE OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY. Russian Journal of Cardiology. 2015;(6):75-80. (In Russ.) https://doi.org/10.15829/1560-4071-2015-6-75-80
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