ß2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies
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ß2-adrenergic receptor polymorphisms, asthma and COPD : two large population-based studies. / Thomsen, M; Nordestgaard, B G; Sethi, A A; Tybjærg-Hansen, A; Dahl, Morten.
In: European Respiratory Journal, Vol. 39, No. 3, 2012, p. 558-66.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2012
N2 - The ß(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 (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/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 FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p <0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV(1) % pred and 6% and 1% reduced FEV(1)/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.
AB - The ß(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 (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/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 FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p <0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV(1) % pred and 6% and 1% reduced FEV(1)/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.
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
VL - 39
SP - 558
EP - 566
JO - The European Respiratory Journal
JF - The European Respiratory Journal
SN - 0903-1936
IS - 3
ER -
ID: 43958380