Risk and severity of COPD is associated with the group-specific component of serum globulin 1F allele

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 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 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.