VITAMIN-D-BINDING PROTEIN VARIANTS AND THE RISK OF COPD

Although the development of chronic obstructive pulmonary disease (COP D) in smokers shows genetic susceptibility, only al-antitrypsin defici ency has been identified as a definite genetic risk factor. There have been three previous studies in which associations between Cc-globulin phenotypes and CORD have been investigated. Although some data sugges t an association, the results were inconclusive. Because smoking is th e major risk factor for COPD, it may have been a confounding factor in previous studies. We have investigated Cc-globulin genotypic frequenc ies among 75 COPD patients and 64 nonobstructed controls. Both groups had significant smoking histories: pack-years (mean +/- SD) of 52 +/- 30 and 48 +/- 27, respectively. The results show that homozygosity for the Gc2 allele is protective against COPD (OR = 0.17, 95% CI = 0.03 t o 0.83). There were no differences between genotypes for lung elastic recoil values or for the level of upstream airway resistance. Gc-globu lin can enhance complement (C5a)-mediated neutrophil chemotaxis. Becau se neutrophils play a role in parenchymal destruction and airway infla mmation, we examined whether Gc-globulin's ability to enhance neutroph il chemotaxis varied with genotype. We found no difference among genot ypes with respect to neutrophil chemotaxis suggesting that the protect ive effect of the Gc2 allele is mediated through a different mechanism .