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Variation in the tumour necrosis factor- gene is not associated with susceptibility to Asian COPD

Dept of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

To the Editors:

In a recent issue of the European Respiratory Journal, Chappell et al. 1 clearly demonstrated that the lack of association with any of the tumour necrosis factor (TNF)- single nucleotide polymorphisms or haplotypes makes it highly unlikely that polymorphisms in this gene play a major role in susceptibility to chronic obstructive pulmonary disease (COPD).

Their sample sizes were sufficient to elucidate association of TNF- gene variations with susceptibility to COPD. However, they neglected the effect of ethnicity differences in genetic susceptibility to COPD. The frequency of the TNF--308*2 allele in Caucasian control populations (10–17%) is higher than that in Asians (0–8%) 1–10.

Genetic susceptibility to COPD is dependent upon the action of several gene polymorphisms, sex, age and ethnicity 2. The TNF- gene is known to have a polymorphic site at position -308. The TNF--308*2 allele, which is associated with a higher level of TNF- production, has been associated with chronic bronchitis, a characteristic part of COPD, in a Taiwanese population 3. However, the association of a polymorphism of TNF- with susceptibility to COPD or to tobacco-related airway inflammation has not yet been confirmed in Asians. It was investigated whether the TNF--308*2 allele was associated with COPD in a Japanese population using a PCR-based genotyping assay 4. The TNF--308*2 allele was found in one (1.9%) out of 53 patients with COPD and in one (1.5%) out of 65 smoker control subjects without COPD 4. The frequency of the major allele, i.e. TNF--308*1, in the smoker control subjects (0.99) was consistent with data reported previously for other Japanese populations, suggesting that the present samples are representative of TNF- gene polymorphism in the Japanese population 5. However, there were no differences between COPD patients and smoker control subjects regarding the allele and genotype frequency of TNF-. Since chronic bronchitis is not exactly the same, in terms of definition and tobacco sensitivity, as pulmonary emphysema, which is a major feature of COPD, it is possible that the TNF- polymorphism is associated with infection-related bronchitis rather than tobacco-smoke-related alveolar wall destruction. However, most of the TNF polymorphism studies investigating COPD susceptibility revealed negative results for various Asian populations (table 1) 6–9. Only one group of authors have insisted that the TNF--308*2 may be partly associated with the extent of emphysematous changes in patients with COPD 9.

View this table: [in this window] [in a new window]   Table 1— Association of tumour necrosis factor(TNF)- gene polymorphism with chronic obstructive pulmonary disease (COPD) in Asian patients in various studies

Thus it is necessary to study polymorphisms within the tumour necrosis factor- gene in a large collection of well-characterised Asian chronic obstructive pulmonary disease patients and control subjects, as in the European Union collaborative project 1. However, these collective data strongly suggest that tumour necrosis factor- gene polymorphism does not play a major role as a genetic risk factor for chronic obstructive pulmonary disease in either Caucasian or Asian individuals. However, the tumour necrosis factor- gene polymorphism may be associated with functional impairment or prognosis in chronic obstructive pulmonary disease.

Statement of interest

None declared.

REFERENCES

1. Chappell S, Daly L, Morgan K, et al. Variation in the tumour necrosis factor gene is not associated with susceptibility to COPD. Eur Respir J 2007;30:810–812.[Free Full Text]
2. Teramoto S. COPD pathogenesis from the viewpoint of risk factors. Intern Med 2007;46:77–79.[CrossRef][Medline] [Order article via Infotrieve]
3. Huang SL, Su CH, Chang SC. Tumor necrosis factor- gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med 1997;156:1436–1439.[Abstract/Free Full Text]
4. Ishii T, Matsuse T, Teramoto S, et al. Neither IL-1β, IL-1 receptor antagonist, nor TNF- polymorphisms are associated with susceptibility to COPD. Respir Med 2000;94:847–851.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
5. Higuchi T, Seki N, Kamizono S, et al. Polymorphism of the 5’-flanking region of the human tumor necrosis factor (TNF)- gene in Japanese. Tissue Antigens 1998;51:605–612.[Web of Science][Medline] [Order article via Infotrieve]
6. Chierakul N, Wongwisutikul P, Vejbaesya S, Chotvilaiwan K. Tumor necrosis factor- gene promoter polymorphism is not associated with smoking-related COPD in Thailand. Respirology 2005;10:36–39.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
7. Jiang L, He B, Zhao MW, Ning LD, Li XY, Yao WZ. Association of gene polymorphisms of tumour necrosis factor- and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing. Chin Med J (Engl) 2005;118:541–547.[Medline] [Order article via Infotrieve]
8. Hegab AE, Sakamoto T, Saitoh W, et al. Polymorphisms of TNF, IL1β, and IL1RN genes in chronic obstructive pulmonary disease. Biochem Biophys Res Commun 2005;329:1246–1252.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
9. Sakao S, Tatsumi K, Igari H, Shino Y, Shirasawa H, Kuriyama T. Association of tumor necrosis factor gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:420–422.[Abstract/Free Full Text]
10. Keating VM, Cave SJ, Henry MJ, et al. A polymorphism in the tumor necrosis factor- gene promoter region may predispose to a poor prognosis in COPD. Chest 2000;118:971–975.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

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