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

Risk and Severity of COPD Is Associated With the Group-Specific Component of Serum Globulin 1F AlleleAlthough the most critical factor for acquiring COPD is cigarette smoking, only 15 to 20% of chronic smokers get this disease. Several epidemiologic studies have suggested familial clustering of the disease. This suggests that the genetic factors are likely to have a role in determining an individual’s susceptibility to COPD. Polymorphisms of several candidate genes have been investigated in relation to the development of COPD. One such candidate is the gene encoding the group-specific component of serum globulin (Gc-globulin), also called vitamin-D-binding protein.

Gc-globulin is a multifunctional, polymorphic, 55-kd protein, whose functions include being a precursor of macrophage-activating factor (MAF), and a co-chemotaxin for phagocytic cells. These-functions suggest a role for this protein in the chronic inflammatory response in the lung. Gc-globulin gene was localized to human chromosome 4q11-q13. There are three common polymorphisms in the structures of Gc-globulin that are encoded by one of three co-dominant alleles of the Gc-globulin gene, Gc*1F, Gc*1S, and Gc*2, and there are > 124 rare variant alleles. Several studies have shown conflicting results in the relationship of Gc-globulin polymorphism and the risk for COPD. Thus, the role of its polymorphism relative to COPD susceptibility is not fully understood.

An important facet in investigating this protein is that the allele proportion varies considerably among populations. In the white population, the protein is reported to exhibit three major isotypes, namely, Gc-1F, Gc-1S, and Gc-2, with allele frequencies of 0.16, 0.56, and 0.28, respectively, whereas in the Japanese population, the same isotypes occur with the frequency of 0.49, 0.24, and 0.25. Ishii et al showed in the Japanese population that the proportion of Gc*1F homozygotes was significantly higher in patients with COPD than in healthy control subjects. This led us to hypothesize that a significant relationship may exist between Gc-globulin polymorphism and the risk for COPD in the Japanese population.