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Communications to the Editor |

No Association of Tumor Necrosis Factor-α Gene Polymorphism and COPD in Caucasian Smokers and Japanese Smokers FREE TO VIEW

Shinji Teramoto, MD, FCCP; Takeo Ishii, MD
Author and Funding Information

Affiliations: International University of Health and Welfare Department of Internal Medicine San-no Hospital Minato-ku Tokyo, Japan Tokyo University Hospital Tokyo, Japan,  IRCCS Policlinico San Matteo Pavia, Italy Università di Verona, Italy Verona, Italy

Correspondence to: Shinji Teramoto, MD, FCCP, Department of Internal Medicine, San-no Hospital, 8-5-35 Akasaka, Minato-ku, Tokyo, Japan 107-0052; e-mail: Shinji-tky@umin.ac.jp



Chest. 2001;119(1):315-316. doi:10.1378/chest.119.1.315
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Published online

To the Editor:

In a recent issue of CHEST (April 2000), Patuzzo et al1 demonstrated that tumor necrosis factor (TNF) gene polymorphism does not seem to play a role as genetic risk factor in COPD and bronchiectasis in Caucasoid individuals.

COPD and bronchiectasis are characterized by airway inflammation. Because proinflammatory cytokines, interleukin-1β and TNF-α, are known to enhance bacterial proliferation,2and because the gene expression of the cytokines is increased in the airways of the patients with COPD,3the genetic regulation of TNF-α production through transcriptional and posttranscriptional levels may affect individual susceptibility to COPD in response to tobacco smoke.4

TNF-α gene is known to have the 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, one characteristic part of COPD, in a Taiwanese population.5 However, the association of polymorphism of TNF-α with susceptibility to COPD or to tobacco-related airway inflammation has not been yet confirmed in Asians. We investigated whether the association of TNF-308*2 allele has an association with COPD in a Japanese population by using polymerase chain reaction-based genotyping assay.67 The TNF-308*2 allele was found in 1 of 53 patients with COPD (1.9%) and in 1 of 65 smoker control subjects without COPD (1.5%).7The frequency of the major allele, ie TNF-308*1, in the smoker control subjects (0.99) was consistent with the previously reported data in other Japanese populations,8 suggesting that our samples represent the TNF gene polymorphism of the Japanese population. However, there were no differences between COPD patients and smoker control subjects in the allele and genotype frequency of TNF-α. Because chronic bronchitis is not exactly the same in terms of definition and tobacco sensitivity as the pulmonary emphysema, which is a major feature of COPD, it is possible that the TNF-α polymorphism is associated with infection-related bronchitis rather than tobacco smoke-related alveolar wall destruction. However, the study by Patuzzo and coworkers1 has wisely revealed that TNF-α polymorphism is not associated with disseminated bronchiectasis, which is related to chronic bacterial infection of lower airways. Furthermore, a study by a group in the United Kingdom9 has demonstrated that there are no differences in the allele and genotype frequencies of TNF-α among COPD patients, age-matched current smokers without COPD, and age-matched ex-smokers. That study also reported that TNF gene polymorphism was not associated with the indexes of airflow obstruction or gas transfer in COPD patients.9

Considered together, the authors’ conclusion that “TNF gene polymorphism does not seem to play a role as a genetic risk factor in COPD and bronchiectasis in Caucasoid individuals” could be extended in an Asian population. It is reasonable, therefore, to assume that there is no significant association of TNF-α gene polymorphism and COPD in either Caucasians or Asians.

References

Patuzzo, C, Gilè, LS, Zorzetto, M, et al (2000) Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis.Chest117,1353-1358. [CrossRef] [PubMed]
 
Meduri, GU, Kanangat, MS, Stefan, J, et al Cytokines IL-1β, IL-6, and TNF-α enhancein vitrogrowth of bacteria.Am J Respir Crit Care Med1999;160,961-967. [PubMed]
 
Muellar, R, Chanez, P, Campbell, AM, et al Different cytokine patterns in bronchial biopsies in asthma and chronic bronchitis.Respir Med1996;90,79-85. [CrossRef] [PubMed]
 
Sandford, AJ, Weir, TD, Pare, PD Genetic risk factors for chronic obstructive pulmonary disease.Eur Respir J1997;10,1380-1391. [CrossRef] [PubMed]
 
Huang, S-L, Su, CH, Chang, SC Tumor necrosis factor-α gene polymorphism in chronic bronchitis.Am J Respir Crit Care Med1997;156,1436-1439. [PubMed]
 
Ishii, T, Matsuse, T, Teramoto, S, et al Glutathione S-transferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease.Thorax1999;54,693-696. [CrossRef] [PubMed]
 
Ishii, T, Matsuse, T, Teramoto, S, et al Neither IL-1β IL-1 receptor antagonist, nor TNF-α polymorphisms are associated with susceptibility to COPD.Respir Med2000;94,847-851. [CrossRef] [PubMed]
 
Higuchi, T, Seki, N, Kamizono, S, et al Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-α gene in Japanese.Tissue Antigens1998;51,605-612. [CrossRef] [PubMed]
 
Higham, MA, Pride, NB, Alikhan, A, et al Tumor necrosis factor-α gene promoter polymorphism in chronic obstructive pulmonary disease.Eur Respir J2000;15,281-284. [CrossRef] [PubMed]
 
To the Editor:

We wish to thank Drs. Teramoto and Ishii for their interesting comments on our article.1Their findings2and a recently published investigation in English subjects3 add to our knowledge of the distribution, among varying ethnic groups, of the tumor necrosis factor-α gene promoter polymorphism and of its relationship with susceptibility to COPD in smokers. We also agree with Drs. Teramoto and Ishii that this polymorphism seems not to play a major role in either Caucasian or Asian subjects.

We also thank Drs. Teramoto and Ishii, as their letter addresses two major points for genetic investigations. First, it is extremely important to study multiple, well-defined, ethnic populations, since differing genetic backgrounds may account for the increased prevalence of disease in varying ethnic groups. Findings become especially relevant if they are confirmed in independent studies, extending beyond geographic boundaries. In this framework, there are clear lessons from genetic investigations of sarcoidosis.4Second, COPD is a term referring to “ . . . a spectrum of chronic respiratory disease. . . . ”5 From a genetic point of view, this is an extremely unfavorable condition, because lack of a clearly defined phenotype greatly reduces the chance for success of an association study with candidate genes. A possible future strategy for genetic studies will be to identify better defined phenotypes within the COPD group and to verify them at a gene level.

References
Patuzzo, C, Gilè, LS, Zorzetto, M, et al Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis.Chest2000;117,1353-1358. [CrossRef] [PubMed]
 
Ishii, T, Matsuse, T, Teramoto, S, et al Neither 1L-1β, IL-1 receptor antagonist, nor TNFα polymorphisms are associated with susceptibility to COPD.Respir Med2000;94,847-851. [CrossRef] [PubMed]
 
Higham, MA, Pride, NB, Alikhan, A, et al Tumor necrosis factor-α gene promoter polymorphism in chronic obstructive pulmonary disease.Eur Respir J2000;15,281-284. [CrossRef] [PubMed]
 
Luisetti, M, Beretta, A, Casali, L Genetic aspects in sarcoidosis.Eur Respir J2000;16,768-780. [CrossRef] [PubMed]
 
Ferguson, GT, Cherniack, RM Current Concepts. Management of chronic obstructive pulmonary disease.N Engl J Med1993;328,1017-1022. [CrossRef] [PubMed]
 

Figures

Tables

References

Patuzzo, C, Gilè, LS, Zorzetto, M, et al (2000) Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis.Chest117,1353-1358. [CrossRef] [PubMed]
 
Meduri, GU, Kanangat, MS, Stefan, J, et al Cytokines IL-1β, IL-6, and TNF-α enhancein vitrogrowth of bacteria.Am J Respir Crit Care Med1999;160,961-967. [PubMed]
 
Muellar, R, Chanez, P, Campbell, AM, et al Different cytokine patterns in bronchial biopsies in asthma and chronic bronchitis.Respir Med1996;90,79-85. [CrossRef] [PubMed]
 
Sandford, AJ, Weir, TD, Pare, PD Genetic risk factors for chronic obstructive pulmonary disease.Eur Respir J1997;10,1380-1391. [CrossRef] [PubMed]
 
Huang, S-L, Su, CH, Chang, SC Tumor necrosis factor-α gene polymorphism in chronic bronchitis.Am J Respir Crit Care Med1997;156,1436-1439. [PubMed]
 
Ishii, T, Matsuse, T, Teramoto, S, et al Glutathione S-transferase P1 (GSTP1) polymorphism in patients with chronic obstructive pulmonary disease.Thorax1999;54,693-696. [CrossRef] [PubMed]
 
Ishii, T, Matsuse, T, Teramoto, S, et al Neither IL-1β IL-1 receptor antagonist, nor TNF-α polymorphisms are associated with susceptibility to COPD.Respir Med2000;94,847-851. [CrossRef] [PubMed]
 
Higuchi, T, Seki, N, Kamizono, S, et al Polymorphism of the 5′-flanking region of the human tumor necrosis factor (TNF)-α gene in Japanese.Tissue Antigens1998;51,605-612. [CrossRef] [PubMed]
 
Higham, MA, Pride, NB, Alikhan, A, et al Tumor necrosis factor-α gene promoter polymorphism in chronic obstructive pulmonary disease.Eur Respir J2000;15,281-284. [CrossRef] [PubMed]
 
Patuzzo, C, Gilè, LS, Zorzetto, M, et al Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis.Chest2000;117,1353-1358. [CrossRef] [PubMed]
 
Ishii, T, Matsuse, T, Teramoto, S, et al Neither 1L-1β, IL-1 receptor antagonist, nor TNFα polymorphisms are associated with susceptibility to COPD.Respir Med2000;94,847-851. [CrossRef] [PubMed]
 
Higham, MA, Pride, NB, Alikhan, A, et al Tumor necrosis factor-α gene promoter polymorphism in chronic obstructive pulmonary disease.Eur Respir J2000;15,281-284. [CrossRef] [PubMed]
 
Luisetti, M, Beretta, A, Casali, L Genetic aspects in sarcoidosis.Eur Respir J2000;16,768-780. [CrossRef] [PubMed]
 
Ferguson, GT, Cherniack, RM Current Concepts. Management of chronic obstructive pulmonary disease.N Engl J Med1993;328,1017-1022. [CrossRef] [PubMed]
 
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