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

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


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 objective: 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.

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 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.

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 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).

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

MeSH terms

  • Aged
  • Alleles
  • Female
  • Forced Expiratory Volume
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lung / diagnostic imaging
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Pulmonary Disease, Chronic Obstructive / diagnostic imaging
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Tomography, X-Ray Computed
  • Vitamin D-Binding Protein / genetics*


  • Vitamin D-Binding Protein