β₂-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies

Abstract

The β₂-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD).

We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism.

We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV₁) % predicted (trend p=0.01) and FEV₁/forced vital capacity (FVC) (p=0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV₁ % pred and FEV₁/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05–2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV₁ % pred (p=0.04) and FEV₁/FVC (p<0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV₁ % pred and 6% and 1% reduced FEV₁/FVC, respectively, compared with noncarriers. The odds ratios for COPD in Thr164Ile homozygotes and heterozygotes were 4.53 (95% CI 1.54–13.3) and 1.07 (95% CI 0.92–1.25), respectively.

Our results suggest that ADRB2 Thr164Ile is associated with reduced lung function and increased risk of COPD in the general population.