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Gene Polymorphism and COPD in Caucasian Smokers and Japanese Smokers
International University of Health and Welfare Department of Internal Medicine San-no Hospital Minato-ku Tokyo, Japan Tokyo University Hospital Tokyo, Japan
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{at}umin.ac.jp
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-1ß and TNF-
, are
known to enhance bacterial proliferation,2
and because the
gene expression of the cytokines is increased in the airways of the
patients with COPD,3
the genetic regulation of TNF-
production through transcriptional and posttranscriptional levels may
affect individual susceptibility to COPD in response to tobacco
smoke.4
TNF- 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- 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.6
7
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%).7
The 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-. 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- 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- 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-
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- gene polymorphism and
COPD in either Caucasians or Asians.
References
enhance in vitro growth of bacteria. Am J Respir Crit Care Med 160,961-967 gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med 156,1436-1439 polymorphisms are associated with susceptibility to COPD. Respir Med 94,847-851[CrossRef][ISI][Medline]
gene in Japanese. Tissue Antigens 51,605-612[ISI][Medline]
gene promoter polymorphism in chronic obstructive pulmonary disease. Eur Respir J 15,281-284[Abstract]
IRCCS Policlinico San Matteo Pavia, Italy Università di Verona, Italy Verona, Italy
Correspondence to: Dr. Maurizio Luisetti, Laboratorio di Biochimica e Genetica, Clinica di Malattie dell’Apparato Respiratorio, IRCCS Policlinico San Matteo, Via Taramelli 5, 27100 Pavia, Italy; e-mail maurizio.luisetti@tin.it
To the Editor:
We wish to thank Drs. Teramoto and Ishii for their interesting
comments on our article.1
Their findings2
and
a recently published investigation in English subjects3
add to our knowledge of the distribution, among varying ethnic groups,
of the tumor necrosis factor- 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.4 Second, 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
polymorphisms are associated with susceptibility to COPD. Respir Med 94,847-851
gene promoter polymorphism in chronic obstructive pulmonary disease. Eur Respir J 15,281-284
This article has been cited by other articles:
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  S. Teramoto, T. Ishii, H. Yamamoto, Y. Yamaguchi, T. Matsuse, and N. A. Molfino Xenobiotic Enzymes and Genetics of COPD Chest, January 1, 2005; 127(1): 408 - 409. [Full Text] [PDF]
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 S. I. Rennard Antiinflammatory Therapies Other Than Corticosteroids Proceedings of the ATS, November 1, 2004; 1(3): 282 - 287. [Abstract] [Full Text] [PDF]
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 S. Teramoto, H. Kume, T. Matsuse, T. Ishii, and Y. Inoue Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and gene polymorphisms Eur. Respir. J., December 1, 2001; 18(6): 1077 - 1077. [Full Text] [PDF]
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