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

^* From the Association of Non-University Pulmonary Specialist Physicians Affiliated to the Chiba University School of Medicine, Department of Respirology (B2) [Drs. Sakao, Tatsumi, Igari, Watanabe, and Kuriyama], and Molecular Virology (E2) [Drs. Shino and Shirasawa], Graduate School of Medicine, Chiba University, Chiba, Japan.

Correspondence to: Seiichiro Sakao, MD, Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan; e-mail: sakao{at}virolo3.m.chiba-u.ac.jp

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 and those with a visual score 11. A polymerase chain reaction-based assay was developed to determine the TNF- genotype (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 (0.90/0.10) 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--308 allele 2 may be partly associated with the extent of emphysematous changes in patients with COPD.

Key Words: apoptosis • COPD • emphysema • tumor necrosis factor-

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