ß2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies

TY - JOUR

T1 - ß2-adrenergic receptor polymorphisms, asthma and COPD

T2 - two large population-based studies

AU - Thomsen, M

AU - Nordestgaard, B G

AU - Sethi, A A

AU - Tybjærg-Hansen, A

AU - Dahl, Morten

PY - 2012/3/1

Y1 - 2012/3/1

N2 - The β 2-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. Copyright

AB - The β 2-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. Copyright

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Asthma

KW - Denmark

KW - Female

KW - Gene Frequency

KW - Humans

KW - Incidence

KW - Lung

KW - Male

KW - Middle Aged

KW - Polymorphism, Genetic

KW - Prevalence

KW - Pulmonary Disease, Chronic Obstructive

KW - Receptors, Adrenergic, beta-2

KW - Young Adult

U2 - 10.1183/09031936.00023511

DO - 10.1183/09031936.00023511

M3 - Journal article

C2 - 22075484

SN - 0904-1850

VL - 39

SP - 558

EP - 566

JO - Acta tuberculosea Scandinavica

JF - Acta tuberculosea Scandinavica

IS - 3

ER -