The ß2-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,Gln27Glu) are associated with 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 associated with reduced FEV1%predicted (trend:p=0.01) and FEV1/FVC (p=0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV1%predicted 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%predicted (p=0.04) and FEV1/FVC (p