Format

Send to

Choose Destination
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.

Author information

1
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
2
Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
3
Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
4
Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
5
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
6
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
7
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
8
Department of Internal Medicine, Ajou University Hospital, Suwon, Korea.
9
Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
10
Department of Clinical Pharmacy, College of Pharmacy, The Catholic University of Korea, Seoul, Korea.
11
Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.

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 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

PMID:
26879662
PMCID:
PMC4773723
DOI:
10.3904/kjim.2015.043
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Publishing M2Community Icon for PubMed Central
Loading ...
Support Center