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Tuesday 13 November 2007

{beta}2-Adrenergic Receptor Genetic Polymorphisms and Short-term Bronchodilator Responses in Patients With COPD.

By: Hizawa N, Makita H, Nasuhara Y, Betsuyaku T, Itoh Y, Nagai K, Hasegawa M, Nishimura M.

Chest 2007 Nov;132(5):1485-92

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 beta(2)-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to beta(2)-agonists; however, the effects of these polymorphisms on responses to beta(2)-agonists in patients with COPD is unknown. OBJECTIVE: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled beta(2)-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 beta(2)-agonist inhalation. The mean (+/-SD) log (postbronchodilator FEV(1) - prebronchodilator FEV(1)) 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 beta(2)-agonists in patients with COPD.

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