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)-alpha 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-alpha gene has been associated with alteration of TNF-alpha 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 and those with a visual score greater than or equal to11. A polymerase chain reaction-based assay was developed to determine the TNF-alpha genotype (TNF-alpha-308*1/2) between subjects with high and low visual scores on chest CT scans. Results: The TNF-alpha-308*1/2 allele frequency, tended to differ between patients with a visual score < 11 (0.90/0.10) and those with a visual score greater than or equal to 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-alpha-308 allele 2 may be partly associated with the extent of emphysematous changes in patients with COPD.