The long-term prognosis of patients with heart failure and the gene polymorphism Gln27Glu of β2-adrenoreceptors

Authors

  • Sergiy Pyvovar Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039, Ukraine https://orcid.org/0000-0003-3446-2767
  • Yuriy Rudyk Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039, Ukraine https://orcid.org/0000-0002-3363-868X
  • Irina Kravchenko Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039, Ukraine https://orcid.org/0000-0003-3446-2767
  • Tatyana Lozyk Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039, Ukraine https://orcid.org/0000-0001-8188-1898

DOI:

https://doi.org/10.15587/2519-4798.2018.143009

Keywords:

heart failure, clinical course, atrial fibrillation, polymorphism, gene, β1-adrenergic receptors, β2-adrenergic receptors

Abstract

The aim: to determine the influence of Gln27Glu polymorphism of the β2-adrenergic receptor gene on the long-term prognosis of patients with heart failure.

Material and methods. The study included 200 patients with heart failure. The clinical course of the disease was evaluated and a genetic study of Gln27Glu polymorphism of the β2-adrenergic receptor gene was done. The material for molecular-genetic research was peripheral blood leukocytes of patients. Isolation of genomic DNA from blood leukocytes for molecular genetic studies was carried out using a commercial "DNA-sorb-B" kit in accordance with the instruction for the kit. Primer sequences were used for the polymerase chain reaction.

Results. An analysis of the distribution of genotypes of the polymorphic Gln27Glu locus of the β2-adrenoreceptor gene in patients with heart failure showed that the genotype Gln27Gln occurs in 33 % of cases; Glu27Glu – in 13 %; Gln27Glu – in 54 %. Carriers of the mutant allele (G) of the β2-adrenoreceptor gene have a high incidence of atrial fibrillation (35.6 % vs. 7.7 %) over 3 years of follow-up. Hospitalization (42.0 % versus 19.2 %) and the frequency of reaching the combined end point (hospitalization + death) (54.0 % vs. 30.8 %) are greater among patients who carry the mutated G allele compared to homozygous patients with the "wild" allele C, for 3 years of observation. Polymorphism of the Gln27Glu gene of the β2-adrenoreceptor does not significantly affect the three-year mortality of patients with heart failure.

Conclusions. The carriers of the mutant allele (G) of β2-adrenergic receptors have a high incidence of atrial fibrillation, hospitalization and the achievement of a combined end point (hospitalization + death) for 3 years of observation, compared to homozygous patients with the "wild-type" allele C. The polymorphism of the gene Gln27Glu of the β2-adrenoceptors does not affect the three-year mortality of patients with heart failure

Author Biographies

Sergiy Pyvovar, Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039

PhD, Senior Researcher

Department of Clinical Pharmacology and Pharmacogenetics non Infective Diseases

Yuriy Rudyk, Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039

MD, Senior Researcher, Head of Department

Department of Clinical Pharmacology and Pharmacogenetics non Infective Diseases

Irina Kravchenko, Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039

PhD, Senior Researcher

Department of Clinical Pharmacology and Pharmacogenetics non Infective Diseases

Tatyana Lozyk, Government Institution “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” Maloi L. ave., 2 a, Kharkiv, Ukraine, 61039

Researcher

Department of Clinical Pharmacology and Pharmacogenetics non Infective Diseases

References

  1. Voronkov, L. G., Іl'nits'ka, M. R., Babich, P. M. (2015). Prohnoz patsiyentiv iz khronichnoyu sertsevoyu nedostatnistyu ta systolichnoyu dysfunktsiyeyu livoho shlunochka zalezhno vid danykh neinvazyvnykh metodiv obstezhennya [Prognosis of patients with chronic heart failure and systolic dysfunction of the left ventricle depending on noninvasive survey data]. Ukrainian Therapeutical Journal, 1, 24–31.
  2. Rudyk, Yu. S., Kravchenko, N. A. (2008). Vliyaniye polimorfizma genov adrenoretseptorov na razvitiye serdechno-sosudistoy patologii i effektivnost' β-adrenoblokatorov [Influence of adrenoreceptor gene polymorphism on development cardiovascular pathology and the efficacy of β-adrenoblockers]. Practical agiology, 2, 35–37.
  3. Rudyk, Yu. S. (2009) Khronicheskaya serdechnaya nedostatochnost' i geneticheskiy polimorfizm: rol' β adrenoretseptorov [Chronic heart failure and genetic polymorphism: the role of β adrenergic receptors]. Heart failure, 2, 20–27.
  4. Bielecka-Dabrowa, A., Sakowicz, A., Pietrucha, T., Misztal, M., Chruściel, P., Rysz, J., Banach, M. (2017). The profile of selected single nucleotide polymorphisms in patients with hypertension and heart failure with preserved and mid-range ejection fraction. Scientific Reports, 7 (1), 8934. doi: http://doi.org/10.1038/s41598-017-09564-9
  5. Bristow, M. R., Ginsburg, R., Umans, V., Fowler, M., Minobe, W., Rasmussen, R. et. al. (1986). Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circulation Research, 59 (3), 297–309. doi: http://doi.org/10.1161/01.res.59.3.297
  6. Ma, S. T., Zhao, W., Liu, B., Jia, R. Y., Zhao, C. J., Cui, L. Q. (2015). Association between β1 adrenergic receptor gene Arg389Gly polymorphism and risk of heart failure: a meta-analysis. Genetics and Molecular Research, 14 (2), 5922–5929. doi: http://doi.org/10.4238/2015.june.1.9
  7. Metaxa, S., Missouris, C., Mavrogianni, D., Miliou, A., Oikonomou, E., Toli, E. et. al. (2018). Polymorphism Gln27Glu of β2 Adrenergic Receptors in Patients with Ischaemic Cardiomyopath. Current Vascular Pharmacology, 16 (6), 618–623. doi: http://doi.org/10.2174/1570161115666170919180959
  8. Voronkov, L. H. (Ed.) (2014). Rekomendatsiyi Ukrayinsʹkoyi asotsiatsiyi kardiolohiv z diahnostyky, likuvannya ta profilaktyky sertsevoyi nedostatnosti u doroslykh. Robocha hrupa Ukrayinsʹkoho naukovoho tovarystva kardiolohiv [Recommendations of the Ukrainian Association of Cardiologists on the diagnosis, treatment and prevention of heart failure in adults. Working Group of the Ukrainian Scientific Society of Cardiologists]. Kyiv: Chetverta khvylya, 47.
  9. Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S. et. al. (2016). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2016. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal, 37 (27), 2129–2200. doi: http://doi.org/10.1093/eurheartj/ehw128
  10. Glik, B., Pasternak, Dzh. (2002). Molekulyarnaya bio-tekhnologiya. Printsipy i primeneniye [Molecular biotechnology. Principles and applications]. Moscow: Mir, 589.
  11. Pyvovar, S. M. (2016). Zalezhnistʹ perebihu sertsevoyi nedostatnosti vid polimorfizmu Gln27Glu hena b2-adrenoretseptoriv [Dependence of heart failure on gln27Glu polymorphism of β2-adrenoreceptor gene]. Ukrainian Therapeutical Journal, 3, 50–55.
  12. Hong, S., Song, W., Zushin, P.-J. H., Liu, B., Jedrychowski, M. P., Mina, A. I. et. al. (2018). Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes. Molecular Metabolism, 12, 25–38. doi: http://doi.org/10.1016/j.molmet.2018.03.012
  13. Balligand, J.-L. (2016). Cardiac salvage by tweaking with beta-3-adrenergic receptors. Cardiovascular Research, 111 (2), 128–133. doi: http://doi.org/10.1093/cvr/cvw056
  14. Petersen, L. H., Needham, S. L., Burleson, M. L., Overturf, M. D., Huggett, D. B. (2013). Involvement of β3-adrenergic receptors in in vivo cardiovascular regulation in rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 164 (2), 291–300. doi: http://doi.org/10.1016/j.cbpa.2012.11.001
  15. Bundgaard, H., Liu, C.-C., Garcia, A., Hamilton, E. J., Huang, Y., Chia, K. K. M. et. al. (2010). β (3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification. Circulation, 122 (25), 2699–2708. doi: http://doi.org/10.1161/circulationaha.110.964619
  16. Rozec, B., Erfanian, M., Laurent, K., Trochu, J.-N., Gauthier, C. (2009). Nebivolol, a Vasodilating Selective β1-Blocker, Is a β3-Adrenoceptor Agonist in the Nonfailing Transplanted Human Heart. Journal of the American College of Cardiology, 53 (17), 1532–1538. doi: http://doi.org/10.1016/j.jacc.2008.11.057
  17. McLean, R. C., Baird, S. W., Becker, L. C., Townsend, S. N., Gerstenblith, G., Kass, D. A. et. al. (2012). Response to Catecholamine Stimulation of Polymorphisms of the Beta-1 and Beta-2 Adrenergic Receptors. The American Journal of Cardiology, 110 (7), 1001–1007. doi: http://doi.org/10.1016/j.amjcard.2012.05.029
  18. Milano, C., Allen, L., Rockman, H., Dolber, P., McMinn, T., Chien, K. et. al. (1994). Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. Science, 264 (5158), 582–586. doi: http://doi.org/10.1126/science.8160017
  19. Vardeny, O., Detry, M. A., Moran, J. J. M., Johnson, M. R., Sweitzer, N. K. (2008). The β2 Adrenergic Receptor Gln27Glu Polymorphism Affects Insulin Resistance in Patients With Heart Failure: Possible Modulation by Choice of Beta Blocker. Journal of Cardiovascular Pharmacology, 52 (6), 500–506. doi: http://doi.org/10.1097/fjc.0b013e31818f5739
  20. Moraga, F., Troncoso, R., Mellado, R., Díaz-Araya, G., Vukasovic, J. L., Greig, D. et. al. (2008). Interactions between beta1 and beta2 adrenergic receptor polymorphisms as risk factors for chronic heart failure. Revista Médica de Chile, 136 (11), 1371–1380. doi: http://doi.org/10.4067/s0034-98872008001100002
  21. Brodde, O.-E. (2008). β-1 and β-2 adrenoceptor polymorphisms: Functional importance, impact on cardiovascular diseases and drug responses. Pharmacology & Therapeutics, 117 (1), 1–29. doi: http://doi.org/10.1016/j.pharmthera.2007.07.002
  22. Panebra, A., Wang, W. C., Malone, M. M., Pitter, D. R. G., Weiss, S. T., Hawkins, G. A., Liggett, S. B. (2010). Common ADRB2 Haplotypes Derived from 26 Polymorphic Sites Direct β2-Adrenergic Receptor Expression and Regulation Phenotypes. PLoS ONE, 5 (7), e11819. doi: http://doi.org/10.1371/journal.pone.0011819
  23. Biolo, A., Salvaro, R., Clausell, N., Silvello, D., Santos, K. G., Rohde, L. E. (2010). Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients. Brazilian Journal of Medical and Biological Research, 43 (6), 565–571. doi: http://doi.org/10.1590/s0100-879x2010007500052
  24. Taira, C., Carranza, A., Mayer, M., Di Verniero, C., Opezzo, J., Hocht, C. (2008). Therapeutic Implications of Beta-Adrenergic Receptor Pharmacodynamic Properties. Current Clinical Pharmacology, 3 (3), 174–184. doi: http://doi.org/10.2174/157488408785747719
  25. Wagoner, L. E., Craft, L. L., Zengel, P., McGuire, N., Rathzb, D. A., Dorn, G. W., Liggett, S. B. (2002). Polymorphisms of the β1-adrenergic receptor predict exercise capacity in heart failure. American Heart Journal, 144 (5), 840–846. doi: http://doi.org/10.1067/mhj.2002.125325
  26. Covolo, L., Gelatti, U., Metra, M., Nodari, S., Picciche, A., Pezzali, N. et. al. (2004). Role of beta1- and beta2-adrenoceptor polymorphisms in heart failure: a case-control study. European Heart Journal, 25 (17), 1534–1541. doi: http://doi.org/10.1016/j.ehj.2004.06.015
  27. Matkovich, S. J., Van Booven, D. J., Hindes, A., Kang, M. Y., Druley, T. E., Vallania, F. L. M. et. al. (2010). Cardiac signaling genes exhibit unexpected sequence diversity in sporadic cardiomyopathy, revealing HSPB7 polymorphisms associated with disease. Journal of Clinical Investigation, 120 (1), 280–289. doi: http://doi.org/10.1172/jci39085
  28. Gu, W., Liu, J., Wang, Z., Liu, Y., Wen, S. (2017). ADRB2polymorphisms and dyslipidemia risk in Chinese hypertensive patients. Clinical and Experimental Hypertension, 39 (2), 139–144. doi: http://doi.org/10.1080/10641963.2016.1210625
  29. Lobmeyer, M. T., Gong, Y., Terra, S. G., Beitelshees, A. L., Langaee, T. Y., Pauly, D. F. et. al. (2007). Synergistic polymorphisms of beta(1) and alpha(2c)_adrenergic receptors and the influence on left ventricular ejection fraction response to beta-blocker therapy in heart failure. Pharmacogenetics and Genomics, 17 (4), 277–282. doi: http://doi.org/10.1097/fpc.0b013e3280105245
  30. Zee, R. Y. L., Cook, N. R., Reynolds, R., Cheng, S., Ridker, P. M. (2005). Haplotype Analysis of the β2 Adrenergic Receptor Gene and Risk of Myocardial Infarction in Humans. Genetics, 169 (3), 1583–1587. doi: http://doi.org/10.1534/genetics.104.037812
  31. De Groote, P., Lamblin, N., Helbecque, N., Mouquet, F., Mc Fadden, E., Hermant, X. et. al. (2005). The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure. European Journal of Heart Failure, 7 (6), 966–973. doi: http://doi.org/10.1016/j.ejheart.2004.10.006
  32. Paczkowska, A., Szperl, M., Malek, L., Mazurkiewicz, L., Skora, E. et. al. (2009). Polymorphisms of the beta-1 and beta-2 adrenergic receptors in Polish patients with idiopathic dilated cardiomyopathy. Kardiol Pol, 67, 235–241.
  33. Nguyen, M.-N., Kiriazis, H., Ruggiero, D., Gao, X.-M., Su, Y., Jian, A. et. al. (2015). Spontaneous ventricular tachyarrhythmias in β2-adrenoceptor transgenic mice in relation to cardiac interstitial fibrosis. American Journal of Physiology – Heart and Circulatory Physiology, 309 (5). doi: http://doi.org/10.1152/ajpheart.00405.2015
  34. Kanki, H., Yang, P., Xie, H.-G., Kim, R. B., George, A. L., Roden, D. M. (2002). Polymorphisms in Beta-Adrenergic Receptor Genes in the Acquired Long QT Syndrome. Journal of Cardiovascular Electrophysiology, 13 (3), 252–256. doi: http://doi.org/10.1046/j.1540-8167.2002.00252.x
  35. Lanfear, D. E., Jones, P. G., Marsh, S., Cresci, S., McLeod, H. L. (2005). Beta2-adrenergic receptor genotype and survival among patients receiving beta-blocker therapy after an acute coronary syndrome. Jama, 294 (12), 1526–1533. doi: http://doi.org/10.1001/jama.294.12.1526
  36. Sotoodehnia, N., Siscovick, D. S., Vatta, M., Psaty, B. M., Tracy, R. P., Towbin, J. A. et. al. (2006). Beta2-adrenergic receptor genetic variants and risk of sudden cardiac death. Circulation, 113 (15), 1842–1848. doi: http://doi.org/10.1161/circulationaha.105.582833
  37. Gavin, M. C., Newton-Cheh, C., Gaziano, J. M., Cook, N. R., VanDenburgh, M., Albert, C. M. (2011). A common variant in the β2-adrenergic receptor and risk of sudden cardiac death. Heart Rhythm, 8 (5), 704–710. doi: http://doi.org/10.1016/j.hrthm.2011.01.003
  38. Tseng, Z. H., Aouizerat, B. E., Pawlikowska, L., Vittinghoff, E., Lin, F., Whiteman, D. et. al. (2008). Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease. Heart Rhythm, 5 (6), 814–821. doi: http://doi.org/10.1016/j.hrthm.2008.03.016
  39. Ulucan, C., Cetintas, V., Tetik, A., Eroglu, Z., Kayikcioglu, M., Can, L. H. et. al. (2008). β1and β2-Adrenergic Receptor Polymorphisms and Idiopathic Ventricular Arrhythmias. Journal of Cardiovascular Electrophysiology, 19 (10), 1053–1058. doi: http://doi.org/10.1111/j.1540-8167.2008.01202.x

Published

2018-09-25

How to Cite

Pyvovar, S., Rudyk, Y., Kravchenko, I., & Lozyk, T. (2018). The long-term prognosis of patients with heart failure and the gene polymorphism Gln27Glu of β2-adrenoreceptors. ScienceRise: Medical Science, (6 (26), 4–10. https://doi.org/10.15587/2519-4798.2018.143009

Issue

Section

Medical Science