title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Wook-Jin
authors.initials: WJ
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Hui-Kyung
authors.initials: HK
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
authors.forename: Hong-Seog
authors.initials: HS
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae-Joong
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Ajou University Hospital, Suwon, Korea.
authors.forename: Joon Han
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seok-Min
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sung Cil
authors.initials: SC
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sang-Hong
authors.initials: SH
authors.lastname: Baek
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D017298:Bisoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D010641:Phenotype; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000235:genetics*; D056910:Republic of Korea; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: C547787:ADRB1 protein, human; D058671:Adrenergic beta-1 Receptor Antagonists; D018342:Receptors, Adrenergic, beta-1; D017298:Bisoprolol
keywords: Beta-blocker; Heart failure; Polymorphism; Receptors, adrenergic, beta