Korean J Intern Med.
2016 Mar;31(2):277-287. 10.3904/kjim.2015.043.
Impact of the beta-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between beta adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study
- Affiliations
-
- 1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- 2Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
- 3Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
- 4Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
- 5Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
- 6Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- 7Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- 8Department of Internal Medicine, Ajou University Hospital, Suwon, Korea.
- 9Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
- 10Department of Clinical Pharmacy, College of Pharmacy, The Catholic University of Korea, Seoul, Korea.
- 11Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. whitesh@catholic.ac.kr
- KMID: 2373803
- DOI: http://doi.org/10.3904/kjim.2015.043
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 +/- 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 beta-blocker therapy according to genotype.
MeSH Terms
-
Adrenergic beta-1 Receptor Antagonists/adverse effects/*therapeutic use
Adult
Aged
Bisoprolol/adverse effects/*therapeutic use
Female
Gene Frequency
Genotype
Heart Failure/diagnosis/*drug therapy/*genetics/physiopathology
Heart Rate/drug effects
Humans
Male
Maximum Tolerated Dose
Middle Aged
Pharmacogenomic Testing
Phenotype
*Polymorphism, Genetic
Precision Medicine
Receptors, Adrenergic, beta-1/*drug effects/*genetics
Republic of Korea
Stroke Volume/drug effects
Time Factors
Treatment Outcome
Ventricular Function, Left/drug effects
Ventricular Remodeling/drug effects
Adrenergic beta-1 Receptor Antagonists
Bisoprolol
Receptors, Adrenergic, beta-1
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