Polymorphisms of the ß2 adrenoreceptor gene in chronic obstructive pulmonary disease

Background: The ß2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease (COPD). Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the ß2-adrenergic receptor (ADRB2) gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ß2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that ß2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity.

Methods: We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and ß2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction (PCR).

Results: In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers (29.47% COPD versus 18.18% controls, p = 0.026). All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ß2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations (≥ 3 hospitalizations within the last 3 years) nor for disease severity (FEV1 ≤ 30% predicted).

Conclusion: Our study suggests that the Gly16 allele of the ß2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.