Chest
Volume 122, Issue 2, August 2002, Pages 416-420
Journal home page for Chest

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

https://doi.org/10.1378/chest.122.2.416Get rights and content

Study objectives

Alveolar septal cell apoptosis may contribute to the pathogenesis of emphysema. Because tumor necrosis factor (TNF)-α 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-α gene has been associated with alteration of TNF-α 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 ≥ 11. A polymerase chain reaction-based assay was developed to determine the TNF-α genotype (TNF-α-308*1/2) between subjects with high and low visual scores on chest CT scans.

Results

The TNF-α-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 ≥ 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-α-308 allele 2 may be partly associated with the extent of emphysematous changes in patients with COPD.

Section snippets

Subjects

The subjects consisted of 84 patients with cigarette smoking-related COPD who underwent HRCT, recruited from the Respiratory Outpatient Department of Chiba University Hospital and affiliated hospitals. COPD was diagnosed on the basis of history, physical examination, and spirometric data, according to the American Thoracic Society guidelines.18 Pulmonary function tests were performed to determine FVC and FEV1 using a standard spirometer (Fudac-60; Fukuda Denshi; Tokyo, Japan) in the standing

Results

Fifty-three men and 31 women were recruited to the cigarette smoking-related COPD group. Age, smoking history, and pulmonary function data of COPD patients are summarized in Table 1. COPD patients were classified by the median visual score: those with a visual score ≥ 11 and those with a visual score < 11. No significant differences were observed in age or smoking history between patients with a visual score ≥ 11 and patients with a visual score < 11. FEV1/FVC and FEV1 percent predicted were

Discussion

In the present study, we compared the frequency of a polymorphism in the promoter region of the TNF-α gene (designated TNF-α-308*1/2) in Japanese patients with cigarette smoking-related COPD showing severe (visual score ≥ 11) and mild or moderate emphysematous changes (visual score < 11). The ages and smoking habits were similar between these two groups. The frequency of the TNF-α-308*2 allele tended to be higher in patients with a visual score ≥ 11 than in patients with a visual score < 11 (p

ACKNOWLEDGMENT

We thank Drs. Katsutoshi Nakayama and Mutsuo Yamaya, Department of Geriatric Medicine, Tohoku University School of Medicine for technical assistance.

References (30)

  • KeatingsVM et al.

    Differences in interleukin-8 and tumor necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma

    Am J Respir Crit Care Med

    (1996)
  • AmraniY et al.

    Activation of the TNFα-p55 receptor induces myocyte proliferation and modulates agonist-evoked calcium transients in cultured human tracheal smooth muscle cells

    Am J Respir Cell Mol Biol

    (1996)
  • EmalaCW et al.

    TNF-α inhibits isoproterenol-stimulated adenylyl cyclase activity in cultured airway smooth muscle cells

    Am J Physiol

    (1997)
  • TepperCG et al.

    Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity

    Proc Natl Acad Sci U S A

    (1995)
  • WilsonAG et al.

    Effects of a polymorphism in the human tumor necrosis factor α promoter on transcription activation

    Proc Natl Acad Sci U S A

    (1997)
  • Cited by (76)

    • TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

      2010, Pulmonary Pharmacology and Therapeutics
      Citation Excerpt :

      TNF-α has been shown to correlate with body mass index (BMI) and cigarette smoke exposure [71,72] and other inflammatory mediators [73] in COPD. A polymorphism of the promoter region of the TNF-α gene has been implicated in the occurrence, severity, and mortality risk of COPD [74–76]. Intriguingly, TNF-α levels in sputum increase significantly during acute exacerbations of COPD [77,78].

    • CT scanning-based phenotypes vary with ADRB2 polymorphisms in chronic obstructive pulmonary disease

      2009, Respiratory Medicine
      Citation Excerpt :

      Genetic variability in COPD patients might explain persistent inflammation and the varying degrees of involvement of airway and parenchyma. To date, there have been several reports regarding the association of CT phenotypes and particular genotypes.7–9 The phenotypes associated with particular genes are mainly the severity of emphysema and emphysema distribution.

    View all citing articles on Scopus

    This study was in part supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science, and Culture, and a research grant by Respiratory Failure Research Group from the Ministry of Health and Welfare, Japan.

    View full text