RT Journal Article SR Electronic T1 β2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 558 OP 566 DO 10.1183/09031936.00023511 VO 39 IS 3 A1 M. Thomsen A1 B.G. Nordestgaard A1 A.A. Sethi A1 A. Tybjærg-Hansen A1 M. Dahl YR 2012 UL http://erj.ersjournals.com/content/39/3/558.abstract AB 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.