Association of tumor necrosis factor-alpha gene promoter polymorphism with low attenuation areas on high-resolution CT in patients with COPD

Chest. 2002 Aug;122(2):416-20. doi: 10.1378/chest.122.2.416.


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 > or = 11. 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 > or = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Female
  • Humans
  • Lung / diagnostic imaging*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Pulmonary Disease, Chronic Obstructive / diagnostic imaging
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Emphysema / diagnostic imaging
  • Pulmonary Emphysema / genetics*
  • Smoking / epidemiology
  • Tomography, X-Ray Computed*
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha