Korean J Intern Med. 2016 Mar;31(2):277-87. doi: 10.3904/kjim.2015.043. Epub 2016 Feb 16.
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.
The Korean journal of internal medicine
Hae-Young Lee, Wook-Jin Chung, Hui-Kyung Jeon, Hong-Seog Seo, Dong-Ju Choi, Eun-Seok Jeon, Jae-Joong Kim, Joon Han Shin, Seok-Min Kang, Sung Cil Lim, Sang-Hong Baek
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
- Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- Department of Internal Medicine, Ajou University Hospital, Suwon, Korea.
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
- Department of Clinical Pharmacy, College of Pharmacy, The Catholic University of Korea, Seoul, Korea.
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
PMCID: PMC4773723 DOI: 10.3904/kjim.2015.043
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 β-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 ± 14.3 to 70.0 ± 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 ± 2.62 mg vs. 3.96 ± 2.05 mg, 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 β-blocker therapy according to genotype.
Keywords: Beta-blocker; Heart failure; Polymorphism; Receptors, adrenergic, beta
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