The Korean journal of internal medicine

  • 제31권2호
  • /
  • Pages.277-287
  • /
  • 2016
  • /
  • 1226-3303(pISSN)
  • /
  • 2005-6648(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
권호 표지
DOI QR코드

DOI QR Code

Impact of the β-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study

  • Lee, Hae-Young (Department of Internal Medicine, Seoul National University Hospital) ;
  • Chung, Wook-Jin (Department of Internal Medicine, Gachon University Gil Medical Center) ;
  • Jeon, Hui-Kyung (Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea) ;
  • Seo, Hong-Seog (Department of Internal Medicine, Korea University Guro Hospital) ;
  • Choi, Dong-Ju (Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Jeon, Eun-Seok (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jae-Joong (Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Shin, Joon Han (Department of Internal Medicine, Ajou University Hospital) ;
  • Kang, Seok-Min (Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Lim, Sung Cil (Department of Clinical Pharmacy, College of Pharmacy, The Catholic University of Korea) ;
  • Baek, Sang-Hong (Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • 투고 : 2015.02.22
  • 심사 : 2015.12.11
  • 발행 : 2016.03.01
⟨ 이전 논문 다음 논문 ⟩

초록

Background/Aims: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). Methods: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. Results: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the ${\beta}-1$ adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from $80.8{\pm}14.3$ to $70.0{\pm}15.0$ beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group ($5.26{\pm}2.62mg$ vs. $3.96{\pm}2.05mg$, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. Conclusions: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring ${\beta}-blocker$ therapy according to genotype.

키워드

참고문헌

  1. Rienstra M, Damman K, Mulder BA, Van Gelder IC, Mc-Murray JJ, Van Veldhuisen DJ. Beta-blockers and outcome in heart failure and atrial fibrillation: a meta-analysis. JACC Heart Fail 2013;1:21-28. https://doi.org/10.1016/j.jchf.2012.09.002
  2. Lee SE, Cho HJ, Lee HY, et al. A multicentre cohort study of acute heart failure syndromes in Korea: rationale, design, and interim observations of the Korean Acute Heart Failure (KorAHF) registry. Eur J Heart Fail 2014;16:700-708. https://doi.org/10.1002/ejhf.91
  3. Youn JC, Seo SM, Lee HS, et al. Trends in hospitalized acute myocardial infarction patients with heart failure in Korea at 1998 and 2008. J Korean Med Sci 2014;29:544-549.
  4. Small KM, Wagoner LE, Levin AM, Kardia SL, Liggett SB. Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure. N Engl J Med 2002;347:1135-1142. https://doi.org/10.1056/NEJMoa020803
  5. Borjesson M, Magnusson Y, Hjalmarson A, Andersson B. A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J 2000;21:1853-1858. https://doi.org/10.1053/euhj.1999.1994
  6. Forleo C, Resta N, Sorrentino S, et al. Association of beta-adrenergic receptor polymorphisms and progression to heart failure in patients with idiopathic dilated cardiomyopathy. Am J Med 2004;117:451-458. https://doi.org/10.1016/j.amjmed.2004.04.012
  7. Cresci S, Kelly RJ, Cappola TP, et al. Clinical and genetic modifiers of long-term survival in heart failure. J Am Coll Cardiol 2009;54:432-444. https://doi.org/10.1016/j.jacc.2009.05.009
  8. Cappola TP, Dorn GW 2nd. Clinical considerations of heritable factors in common heart failure. Circ Cardiovasc Genet 2011;4:701-709. https://doi.org/10.1161/CIRCGENETICS.110.959379
  9. Filigheddu F. Genetic prediction of heart failure incidence, prognosis and beta-blocker response. Mol Diagn Ther 2013;17:205-219. https://doi.org/10.1007/s40291-013-0035-6
  10. Liggett SB, Mialet-Perez J, Thaneemit-Chen S, et al. A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proc Natl Acad Sci U S A 2006;103:11288-11293. https://doi.org/10.1073/pnas.0509937103
  11. Liggett SB, Tepe NM, Lorenz JN, et al. Early and delayed consequences of beta(2)-adrenergic receptor overexpression in mouse hearts: critical role for expression level. Circulation 2000;101:1707-1714. https://doi.org/10.1161/01.CIR.101.14.1707
  12. Bruck H, Leineweber K, Temme T, et al. The Arg389Gly beta1-adrenoceptor polymorphism and catecholamine effects on plasma-renin activity. J Am Coll Cardiol 2005;46:2111-2115. https://doi.org/10.1016/j.jacc.2005.08.041
  13. Rochais F, Vilardaga JP, Nikolaev VO, Bunemann M, Lohse MJ, Engelhardt S. Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. J Clin Invest 2007;117:229-235. https://doi.org/10.1172/JCI30012
  14. Fiuzat M, Neely ML, Starr AZ, et al. Association between adrenergic receptor genotypes and beta-blocker dose in heart failure patients: analysis from the HF-ACTION DNA substudy. Eur J Heart Fail 2013;15:258-266. https://doi.org/10.1093/eurjhf/hfs175
  15. Small KM, McGraw DW, Liggett SB. Pharmacology and physiology of human adrenergic receptor polymorphisms. Annu Rev Pharmacol Toxicol 2003;43:381-411. https://doi.org/10.1146/annurev.pharmtox.43.100901.135823
  16. Shin J, Johnson JA. Pharmacogenetics of beta-blockers. Pharmacotherapy 2007;27:874-887. https://doi.org/10.1592/phco.27.6.874
  17. Metra M, Covolo L, Pezzali N, et al. Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovasc Drugs Ther 2010;24:49-60. https://doi.org/10.1007/s10557-010-6220-5
  18. Biolo A, Clausell N, Santos KG, et al. Impact of beta1-adrenergic receptor polymorphisms on susceptibility to heart failure, arrhythmogenesis, prognosis, and response to beta-blocker therapy. Am J Cardiol 2008;102:726-732. https://doi.org/10.1016/j.amjcard.2008.04.070
  19. Mahesh Kumar KN, Ramu P, Rajan S, Shewade DG, Balachander J, Adithan C. Genetic polymorphisms of beta1 adrenergic receptor and their influence on the cardiovascular responses to metoprolol in a South Indian population. J Cardiovasc Pharmacol 2008;52:459-466. https://doi.org/10.1097/FJC.0b013e31818d3878
  20. Wood AJ, Zhou HH. Ethnic differences in drug disposition and responsiveness. Clin Pharmacokinet 1991;20:350-373. https://doi.org/10.2165/00003088-199120050-00002
  21. Lee HY, Cho HJ, Kim HY, et al. Effects of intensive versus mild lipid lowering by statins in patients with ischemic congestive heart failure: Korean Pitavastatin Heart Failure (SAPHIRE) study. Korean J Intern Med 2014;29:754-763. https://doi.org/10.3904/kjim.2014.29.6.754
  22. Muszkat M. Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9. Clin Pharmacol Ther 2007;82:215-218. https://doi.org/10.1038/sj.clpt.6100142
  23. Ogimoto A, Okayama H, Nagai T, et al. Impact of synergistic polymorphisms in adrenergic receptor-related genes and cardiovascular events in patients with dilated cardiomyopathy. Circ J 2012;76:2003-2008. https://doi.org/10.1253/circj.CJ-11-1014
  24. Brodde OE. Beta-1 and beta-2 adrenoceptor polymorphisms: functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 2008;117:1-29. https://doi.org/10.1016/j.pharmthera.2007.07.002
  25. Azuma J, Nonen S. Chronic heart failure: beta-blockers and pharmacogenetics. Eur J Clin Pharmacol 2009;65:3-17. https://doi.org/10.1007/s00228-008-0566-7
  26. Yogev D, Basheer M, Blotnick S, Caraco Y, Muszkat M. Effects of sex and the common ADRB1 389 genetic polymorphism on the hemodynamic response to dobutamine. Pharmacogenet Genomics 2015;25:555-563.
  27. Cullington D, Goode KM, Clark AL, Cleland JG. Heart rate achieved or beta-blocker dose in patients with chronic heart failure: which is the better target? Eur J Heart Fail 2012;14:737-747. https://doi.org/10.1093/eurjhf/hfs060
  28. Greene SJ, Vaduganathan M, Wilcox JE, et al. The prognostic significance of heart rate in patients hospitalized for heart failure with reduced ejection fraction in sinus rhythm: insights from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) trial. JACC Heart Fail 2013;1:488-496. https://doi.org/10.1016/j.jchf.2013.08.005
  29. Biolo A, Salvaro R, Clausell N, Silvello D, Santos KG, Rohde LE. Impact of beta-2 Thr164Ile and combined beta- adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients. Braz J Med Biol Res 2010;43:565-571. https://doi.org/10.1590/S0100-879X2010007500052
  30. White HL, de Boer RA, Maqbool A, et al. An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study. Eur J Heart Fail 2003;5:463-468. https://doi.org/10.1016/S1388-9842(03)00044-8
  31. Wagoner LE, Craft LL, Zengel P, et al. Polymorphisms of the beta1-adrenergic receptor predict exercise capacity in heart failure. Am Heart J 2002;144:840-846. https://doi.org/10.1067/mhj.2002.125325
  32. Terra SG, Pauly DF, Lee CR, et al. Beta-adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure. Clin Pharmacol Ther 2005;77:127-137. https://doi.org/10.1016/j.clpt.2004.10.006
  33. Chen L, Meyers D, Javorsky G, et al. Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol. Pharmacogenet Genomics 2007;17:941-949. https://doi.org/10.1097/FPC.0b013e3282ef7354
  34. Liu WN, Fu KL, Gao HY, et al. beta1 adrenergic receptor polymorphisms and heart failure: a meta-analysis on susceptibility, response to beta-blocker therapy and prognosis. PLoS One 2012;7:e37659. https://doi.org/10.1371/journal.pone.0037659
  35. Liu J, Liu ZQ, Yu BN, et al. beta1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther 2006;80:23-32. https://doi.org/10.1016/j.clpt.2006.03.004
  36. Terra SG, Hamilton KK, Pauly DF, et al. Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy. Pharmacogenet Genomics 2005;15:227-234. https://doi.org/10.1097/01213011-200504000-00006
  37. Petersen M, Andersen JT, Hjelvang BR, et al. Association of beta-adrenergic receptor polymorphisms and mortality in carvedilol-treated chronic heart-failure patients. Br J Clin Pharmacol 2011;71:556-565. https://doi.org/10.1111/j.1365-2125.2010.03868.x
  38. O'Connor CM, Fiuzat M, Carson PE, et al. Combinatorial pharmacogenetic interactions of bucindolol and beta1, alpha2C adrenergic receptor polymorphisms. PLoS One 2012;7:e44324. https://doi.org/10.1371/journal.pone.0044324
  39. Mesangeau D, Laude D, Elghozi JL. Early detection of cardiovascular autonomic neuropathy in diabetic pigs using blood pressure and heart rate variability. Cardiovasc Res 2000;45:889-899. https://doi.org/10.1016/S0008-6363(99)00406-X

피인용 문헌

  1. Optimal Use of Beta-Blockers for Congestive Heart Failure vol.80, pp.3, 2016, https://doi.org/10.1253/circj.cj-16-0101
  2. Pharmacogenomics of heart failure: a systematic review vol.17, pp.16, 2016, https://doi.org/10.2217/pgs-2016-0118
  3. Clinical utility of sympathetic blockade in cardiovascular disease management vol.15, pp.4, 2016, https://doi.org/10.1080/14779072.2017.1307736
  4. G protein-coupled receptor kinases as therapeutic targets in the heart vol.16, pp.10, 2016, https://doi.org/10.1038/s41569-019-0220-3
  5. Eight immune-related genes predict survival outcomes and immune characteristics in breast cancer vol.12, pp.16, 2016, https://doi.org/10.18632/aging.103753
  6. Pharmacogenetic polymorphisms affecting bisoprolol response vol.142, pp.None, 2021, https://doi.org/10.1016/j.biopha.2021.112069