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Clinical Investigations: COPD |

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F Allele*

Isao Ito; Sonoko Nagai; Yuma Hoshino; Shigeo Muro; Toyohiro Hirai; Mitsuhiro Tsukino; Michiaki Mishima
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*From the Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to: Isao Ito, MD, Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Shogoin-kawaharacho 54, Sakyo-ku, Kyoto, 606-8507, Japan; e-mail: isaoito@kuhp.kyoto-u.ac.jp



Chest. 2004;125(1):63-70. doi:10.1378/chest.125.1.63
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Background: 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.

Study objectives: 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.

Design: Association study.

Subjects and methods: 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 FEV1 (dFEV1) 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.

Results: There was an increased proportion of Gc*1F 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 Gc*1F allele showed a larger dFEV1 (p = 0.01), higher frequency with LAA% > 60% (p = 0.01), and lower mean CT score than patients without this allele (p = 0.03).

Conclusion: Gc-globulin polymorphism is significantly associated with susceptibility to COPD, and also with the severity of the disease.

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