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

We also considered it important to test the contribution of Gc-globulin genotypes to the disease progression or severity in patients with COPD because, to our knowledge, this has not yet been investigated. The annual decline of FEV1 (dFEV1) is often taken to represent progressive airway obstruction and physiologic deterioration in smokers, and as an indication of disease progression in patients with COPD. Sandford et al investigated the relationship between various candidate gene genotypes, including Gc-globulin, and dFEV1 in a population of smokers; no relation was seen between Gc-globulin genotypes and decline in lung function. In addition to the evaluation of airway obstruction, it is also important to evaluate in patients with COPD the severity of parenchymal injury that is termed emphysema. Parameters such as low-attenuation area percentage (LAA%) and mean CT score in high-resolu-tion CT (HRCT) have been shown to be useful in the assessment of emphysema. To test the hypothesis that Gc-globulin polymorphism has an important role in the susceptibility to COPD, we analyzed the polymorphism in patients with COPD and healthy smokers in a sample drawn from the Japanese population. We further examined the correlation between the genotypes and the extent of deterioration in the rate of airflow in patients with COPD represented by dFEV1. The correlation between the genotypes and the extent of emphysema was evaluated by several radiologic parameters assessed by HRCT.

The study subjects for genotyping comprised 103 patients with COPD and 88 healthy smokers. Patients with COPD were recruited consecutively from the COPD clinic of Kyoto University Hospital if they had smoking history of > 20 pack-years. The diagnosis of COPD was made according to the definition provided by the American Thoracic Society. Patients with reversible respiratory symptoms were considered to have a possibility of bronchial asthma and were excluded from the study. Healthy smokers with smoking history of > 20 pack-years were recruited consecutively at the smokers’ clinic of Kyoto Disease Prevention Center (n = 68), or that of Ono Municipal Hospital (n = 20). Subjects were considered healthy smokers if they did not have COPD or other diseases, and their pulmonary function tests showed a FEV1/FVC ratio > 70%. All subjects were of Japanese ancestry. This study was approved by the Ethics Committee of Kyoto University, and written informed consents were obtained from all subjects.