Dept of Clinical Biochemistry, Herlev Hospital, Herlev, Denmark.
Eur Respir J. 2012 Mar;39(3):558-66. doi: 10.1183/09031936.00023511. Epub 2011 Nov 10.
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 (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.
β2-肾上腺素能受体（ADRB2）是气道平滑肌张力的重要调节剂。我们检验了以下假说，即在 ADRB2 基因中存在三个功能性多态性（Thr164Ile、Gly16Arg 和 Gln27Glu）与肺功能降低、哮喘或慢性阻塞性肺疾病（COPD）相关。我们首先对哥本哈根城市心脏研究中的 8971 个人进行了这三种多态性的基因分型。为了验证我们的发现，我们对哥本哈根普通人群研究中的另外 53777 个人进行了 Thr164Ile 多态性的基因分型。我们鉴定了 60910 名 Thr164Ile 非携带者、1822 名杂合子和 16 名纯合子。在哥本哈根城市心脏研究中，Thr164Ile 基因型与用力呼气量（FEV1）%预计值降低相关（趋势 p = 0.01）和 FEV1/用力肺活量（FVC）（p = 0.001）：与非携带者相比，Thr164Ile 杂合子的 FEV1%预计值分别降低了 3%和 2%。Thr164Ile 杂合子的 COPD 比值比为 1.46（95%可信区间 1.05-2.02）。在哥本哈根普通人群研究中，Thr164 基因型与 FEV1%预计值降低相关（p = 0.04）和 FEV1/FVC 降低相关（p < 0.001）：与非携带者相比，Thr164Ile 纯合子和杂合子的 FEV1%预计值分别降低了 7%和 1%，FEV1/FVC 分别降低了 6%和 1%。Thr164Ile 纯合子和杂合子的 COPD 比值比分别为 4.53（95%可信区间 1.54-13.3）和 1.07（95%可信区间 0.92-1.25）。我们的结果表明，ADRB2 Thr164Ile 与肺功能降低和普通人群 COPD 风险增加相关。
