Ito Isao, Nagai Sonoko, Hoshino Yuma, Muro Shigeo, Hirai Toyohiro, Tsukino Mitsuhiro, Mishima Michiaki
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Chest. 2004 Jan;125(1):63-70. doi: 10.1378/chest.125.1.63.
The finding that only 15 to 20% of cigarette smokers acquire COPD suggests that there is a genetic predisposition to the disease. Genetic polymorphism of the group-specific component of serum globulin (Gc-globulin), also known as vitamin-D-binding protein, is considered one of the candidates for the susceptibility to COPD. However, the role of Gc-globulin polymorphism in the development of COPD remains inconclusive.
s: To determine whether Gc-globulin gene polymorphism plays a role in the development of COPD in the Japanese population, and whether it is associated with the physiologic deterioration in COPD, and its radiologically detectable correlates.
Association study.
One hundred three patients with COPD and 88 healthy smokers sampled from the Japanese population were genotyped for Gc-globulin by the restriction fragment-length polymorphism method. Based on the results of the genotyping, we investigated the relationship between Gc-globulin polymorphism and a physiologic/radiologic indicator of lung function, namely, the annual decline of FEV(1) (dFEV(1)) in 86 patients with COPD and 21 healthy smokers. Additionally, high-resolution CT parameters such as low-attenuation area percentage (LAA%) and average CT number (mean CT score) were measured in 85 patients with COPD.
There was an increased proportion of Gc1F homozygotes in the patients with COPD (32%) compared with the healthy smokers (17%) [p = 0.01; odds ratio, 2.3; 95% confidence interval, 1.2 to 4.6]. Patients with COPD and the Gc1F allele showed a larger dFEV(1) (p = 0.01), higher frequency with LAA% > 60% (p = 0.01), and lower mean CT score than patients without this allele (p = 0.03).
Gc-globulin polymorphism is significantly associated with susceptibility to COPD, and also with the severity of the disease.
仅有15%至20%的吸烟者会患上慢性阻塞性肺疾病（COPD），这一发现表明该疾病存在遗传易感性。血清球蛋白组特异性成分（Gc球蛋白）的基因多态性，也被称为维生素D结合蛋白，被认为是COPD易感性的候选因素之一。然而，Gc球蛋白多态性在COPD发生发展中的作用仍无定论。
确定Gc球蛋白基因多态性在日本人群COPD发生发展中是否起作用，以及它是否与COPD的生理功能恶化及其影像学可检测的相关因素有关。
关联研究。
采用限制性片段长度多态性方法，对从日本人群中抽取的103例COPD患者和88名健康吸烟者进行Gc球蛋白基因分型。根据基因分型结果，我们研究了86例COPD患者和21名健康吸烟者中Gc球蛋白多态性与肺功能的生理/影像学指标（即第1秒用力呼气容积（FEV(1)）的年下降率（dFEV(1)））之间的关系。此外，还对85例COPD患者进行了高分辨率CT参数测量，如低衰减面积百分比（LAA%）和平均CT值（平均CT评分）。
与健康吸烟者（17%）相比，COPD患者中Gc1F纯合子的比例增加（32%）[p = 0.01；优势比，2.3；95%置信区间，1.2至4.6]。与没有该等位基因的患者相比，携带Gc1F等位基因的COPD患者表现出更大的dFEV(1)（p = 0.01）、更高的LAA% > 60%频率（p = 0.01）以及更低的平均CT评分（p = 0.03）。
Gc球蛋白多态性与COPD易感性显著相关，也与疾病严重程度相关。
