β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD

Nobuyuki Hizawa, Hironi Makita, Yasuyuki Nasuhara, Tomoko Betsuyaku, Yoko Itoh, Katsura Nagai, Masaru Hasegawa, Masaharu Nishimura

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Background: COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the β2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to β2-agonists; however, the effects of these polymorphisms on responses to β2- agonists in patients with COPD is unknown. Objective: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled β2-agonists in patients with COPD. Design and Participants: A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. Results: The presence of the Arg16 allele was associated with lower BDRs to β2-agonist inhalation. The mean (±SD) log (postbronchodilator FEV1 - prebronchodilator FEV1) values of Gly16 homozygotes (n = 65), Arg16Gly16 heterozygotes n = 106), and Arg16 homozygotes (n = 75) were 2.19 ± 0.43, 2.09 ± 0.42, and 2.01 ± 0.42, respectively (p < 0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p < 0.01). Conclusion: The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting β2-agonists in patients with COPD.

Original languageEnglish
Pages (from-to)1485-1492
Number of pages8
JournalChest
Volume132
Issue number5
DOIs
Publication statusPublished - 2007 Nov

Keywords

  • Arg16Gly
  • Bronchodilator response
  • COPD
  • Genetic polymorphism
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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