Department of Respiratory Medicine, Hvidovre Hospital, Hvidovre and Amager Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
Thorax. 2019 Oct;74(10):934-940. doi: 10.1136/thoraxjnl-2018-212340. Epub 2019 Sep 3.
Individual susceptibility to exacerbations in chronic obstructive pulmonary disease (COPD) is likely influenced by genetic factors; however, most such variance is unexplained. We hypothesised that β-adrenergic receptor genotypes, Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) influence risk of severe exacerbations in COPD.
Among 96 762 individuals in the Copenhagen General Population Study, we identified 5262 with COPD (forced expiratory volume in one second divided by forced vital capacity, FEV/FVC, below 0.7, FEV less than 80% of predicted value, age above 40 years and no asthma) who had genotyping performed. Severe exacerbations were defined as acute admissions due to COPD during 5 years of follow-up (mean 3.4 years). 923 individuals with COPD diagnosed similarly in the Copenhagen City Heart Study (CCHS) were used for replication analyses.
We recorded 461 severe exacerbations in 5262 subjects. The HRs for severe exacerbations were 1.62 (95% CI 1.30 to 2.03, p=0.00002) for 16Gly/Arg heterozygotes and 1.41 (1.04 to 1.91, p=0.03) for 16Arg homozygotes, compared with 16Gly homozygotes. HRs were 1.35 (1.03 to 1.76, p=0.03) for 27Gln/Glu heterozygotes and 1.49 (1.12 to 1.98, p=0.006) for 27Gln homozygotes, compared with 27Glu homozygotes. Similar trends were observed in the CCHS. Among 27Gln homozygotes only, HRs were 5.20 (1.81 to 14.9, p=0.002) for 16Gly/Arg heterozygotes and 4.03 (1.40 to 11.6, p=0.01) for 16Arg homozygotes, compared with 16Gly homozygotes.
Common β-adrenergic receptor genotypes influence risk of severe exacerbations in COPD, potentially mainly by genetic influence of the 16Arg allele in rs1042713.
个体对慢性阻塞性肺疾病（COPD）恶化的易感性可能受到遗传因素的影响；然而，大多数这种差异尚无法解释。我们假设β-肾上腺素能受体基因型 Gly16Arg（rs1042713，c.46G>A）和 Gln27Glu（rs1042714，c.79C>G）影响 COPD 严重恶化的风险。
在哥本哈根普通人群研究的 96762 名个体中，我们确定了 5262 名患有 COPD（一秒用力呼气量除以用力肺活量，FEV/FVC，低于 0.7，FEV 低于预测值的 80%，年龄大于 40 岁且无哮喘）的个体进行了基因分型。严重恶化定义为在 5 年随访期间（平均 3.4 年）因 COPD 导致的急性入院。在哥本哈根心脏研究（CCHS）中，有 923 名患有类似 COPD 的患者被用于复制分析。
我们在 5262 名患者中记录了 461 例严重恶化事件。与 16Gly 纯合子相比，16Gly/Arg 杂合子的严重恶化风险比为 1.62（95%CI 1.30-2.03，p=0.00002），16Arg 纯合子的风险比为 1.41（1.04-1.91，p=0.03）。与 27Glu 纯合子相比，27Gln/Glu 杂合子的严重恶化风险比为 1.35（95%CI 1.03-1.76，p=0.03），27Gln 纯合子的风险比为 1.49（1.12-1.98，p=0.006）。在 CCHS 中也观察到了类似的趋势。仅在 27Gln 纯合子中，与 16Gly 纯合子相比，16Gly/Arg 杂合子的风险比为 5.20（95%CI 1.81-14.9，p=0.002），16Arg 纯合子的风险比为 4.03（1.40-11.6，p=0.01）。
常见的β-肾上腺素能受体基因型影响 COPD 严重恶化的风险，这可能主要是由于 rs1042713 中 16Arg 等位基因的遗传影响。
