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.
- Author:
Hae Young LEE
1
;
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
Author Information
- Publication Type:Original Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
- Keywords: Heart failure; Beta-blocker; Polymorphism; Receptors, adrenergic, beta
- MeSH: 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
- From:The Korean Journal of Internal Medicine 2016;31(2):277-287
- CountryRepublic of Korea
- Language:English
- 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.
