Beta2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD.
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 beta2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to beta2-agonists; however, the effects of these polymorphisms on responses to beta2-agonists in patients with COPD is unknown.


OBJECTIVE
To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled beta2-agonists in patients with COPD.


METHODS
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 beta2-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).


CONCLUSIONS
The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting beta2-agonists in patients with COPD.
Hizawa
Nobuyuki
N
Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Makita
Hironi
H
Nasuhara
Yasuyuki
Y
Betsuyaku
Tomoko
T
Itoh
Yoko
Y
Nagai
Katsura
K
Hasegawa
Masaru
M
Nishimura
Masaharu
M
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000368:Aged; D000420:Albuterol / Q000627:therapeutic use*; D000483:Alleles; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D003062:Codon; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D003062:Codon; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol