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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)277-287
Number of pages11
JournalKorean Journal of Internal Medicine
Volume31
Issue number2
DOIs
Publication statusPublished - 2016 Mar 1

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Bisoprolol
Adrenergic Receptors
Heart Failure
Genotype
Stroke Volume
Heart Rate
Therapeutics
Brain Natriuretic Peptide
Therapeutic Uses
Gene Frequency
Genes
Research Personnel
Exercise

Keywords

  • Adrenergic
  • Beta
  • Beta-blocker
  • Heart failure
  • Polymorphism
  • Receptors

ASJC Scopus subject areas

  • Internal Medicine

Cite this

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. / Lee, Hae Young; Chung, Wook Jin; Jeon, Hui Kyung; Seo, Hong Seog; Choi, Dong Ju; Jeon, Eun Seok; Kim, Jae Joong; Shin, Joon Han; Kang, Seok Min; Lim, Sung Cil; Baek, Sang Hong.

In: Korean Journal of Internal Medicine, Vol. 31, No. 2, 01.03.2016, p. 277-287.

Research output: Contribution to journalArticle

Lee, Hae Young ; Chung, Wook Jin ; Jeon, Hui Kyung ; Seo, Hong Seog ; Choi, Dong Ju ; Jeon, Eun Seok ; Kim, Jae Joong ; Shin, Joon Han ; Kang, Seok Min ; Lim, Sung Cil ; Baek, Sang Hong. / 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. In: Korean Journal of Internal Medicine. 2016 ; Vol. 31, No. 2. pp. 277-287.
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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.",
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T2 - Association between β adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study

AU - Lee, Hae Young

AU - Chung, Wook Jin

AU - Jeon, Hui Kyung

AU - Seo, Hong Seog

AU - Choi, Dong Ju

AU - Jeon, Eun Seok

AU - Kim, Jae Joong

AU - Shin, Joon Han

AU - Kang, Seok Min

AU - Lim, Sung Cil

AU - Baek, Sang Hong

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AB - 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.

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KW - Beta

KW - Beta-blocker

KW - Heart failure

KW - Polymorphism

KW - Receptors

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