Association of Tumor Necrosis Factor-α Gene Promoter Polymorphism With Low Attenuation Areas on High-Resolution CT in Patients With COPD

Study objectives: Alveolar septal cell apoptosis may contribute to the pathogenesis of emphysema. Because tumor necrosis factor (TNF)- is assumed to play an important role in the induction of apoptosis, and allele 2 of the polymorphism at position 308 in the promoter of the TNF- gene has been associated with alteration of TNF- secretion in vitro, we hypothesized that genotypes containing this allele would show more destructive emphysematous changes of the lung. Design: The percentage ratio of the low attenuation area to the corresponding lung area was evaluated using a visual scoring system for CT findings in patients with COPD (n 84), and these patients were classified into two groups: those with a visual score 11. A polymerase chain reaction-based assay was developed to determine the TNFgenotype (TNF--308*1/2) between subjects with high and low visual scores on chest CT scans. Results: The TNF--308*1/2 allele frequency tended to differ between patients with a visual score 11 (0.81/0.19) [odds ratio, 2.15; 95% confidence interval, 0.87 to 5.30; p 0.09]. Conclusion: These results indicate that the TNF--308 allele 2 may be partly associated with the extent of emphysematous changes in patients with COPD. (CHEST 2002; 122:416 – 420)