Association of beta-2-adrenoceptor polymorphisms and pulmonary function in patients with chronic obstructive pulmonary disease

Abstract

Aims: The Dutch Hypothesis suggests that asthma and chronic obstructive pulmonary disease may share some pathogenic mechanisms. There is considerable evidence that polymorphisms of the β2 adrenoceptor have disease-modifying roles in juvenile onset asthma, determining severity and response to β agonists, but not determining disease susceptibility. There is evidence from family and twin studies to suggest that chronic obstructive pulmonary disease (COPD) also has a significant genetic component. We therefore hypothesized that β2 adrenoceptor polymorphisms would have similar disease modifying roles in patients with COPD. Methods: One hundred and ninety-five COPD subjects and 142 matched controls were recruited. All had detailed clinical phenotyping. Subjects were genotyped for the Agr Gly polymorphism at codon 16, the Gln Glu polymorphism at codon 27, and the SNPC/T-47 promoter polymorphism. Results: In patients with COPD (mean age 67, 57% male), individuals with the homozygous Gly16/homozygous Glu27/homozygous SNP −47*C genotype had significantly worse lung function as measured by forced expiratory volume 1, expressed as a percentage of its predicted value (39.2 compared with 45.8, P = 0.004), and for forced vital capacity (FVC) percent predicted (77.2 compared with 70.4, P = 0.02). The polymorphisms had no effect on disease susceptibility. Conclusion: The Arg16, Gln27, SNPC/T-47 β2 adrenoceptor polymorphisms may have disease modifying roles in patients with COPD.