The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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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)
  • Received : 2015.02.22
  • Accepted : 2015.12.11
  • Published : 2016.03.01
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Abstract

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.

Keywords

References

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