There are several limitations in our study. First, the age and smoking history in pack-years of the control group were not exactly equivalent to the COPD patient group. Considering that some sub jects in the control group might subsequently acquire COPD, with or without additional smoking exposure, the possibility remains that the different background of the two groups could influence the results of the genotyping. Ideally, the age and smoking history of the two groups should be exactly matched. Then the results of genotyping would be more clearly differentiated between the two groups. Secondly, only a small number of smoker control subjects were successfully followed up for > 1 year, and we obtained dFEV1 data in a segment of this group. This was because they stopped visiting the clinic on cessation of smoking. Thirdly, data on HRCT parameters were not collected in the healthy smoker group because the facilities where the healthy smokers were recruited were not equipped with the same imaging technique that was available for the patients with COPD. If healthy smokers with Gc*1F allele could be shown to have larger dFEV1 and higher LAA% than those without the allele, our conclusion that the Gc*1F allele is related to the development of COPD would be more clearly substantiated. The role of this allele in the early development of COPD remains to be investigated. buy prozac online
Though only Gc*1F homozygotes were significantly associated with COPD and not the control subjects, we could not confirm a difference in dFEV1 or HRCT parameters between the patients with COPD and Gc*1F homozygotes and those of Gc*1F heterozygotes. From the data we obtained, we infer that the presence of a single Gc*1F allele caused a rapid decline of FEV1 in patients who already had COPD. However, we were not able to demonstrate that Gc*1F homozygosity was more likely to be associated with further rapid decline of FEV1 than Gc*1F heterozygosity. As mentioned above, if dFEV1 and HRCT parameters were available in a sufficiently large control group, the role of Gc*1F homozygosity or heterozygosity in deterioration of lung function or HRCT findings would have been clearly elucidated.
In conclusion, we showed that the incidence of Gc*1F homozygosity was significantly higher in patients with COPD than in healthy smokers. Patients with COPD and the Gc*1F allele had a faster decline of FEV1 than patients without the allele. Moreover, HRCT parameters indicated that patients with COPD with this allele had a more severe emphysema. The role of Gc-globulin genotypes in acquiring COPD remains to be elucidated.