Association Between Polymorphism Of Tumour

466

A STHMA

Association between polymorphism of tumour
necrosis factor a-308 gene promoter and asthma: a
meta-analysis
J Gao, G Shan, B Sun, P J Thompson, X Gao
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Thorax 2006;61:466–471. doi: 10.1136/thx.2005.051284

See end of article for
authors’affiliations
.......................
Correspondence to:
Dr J Gao, Department of
Respiratory Diseases,
Peking Union Medical
College Hospital, 1
Shuaifuyuan, Dongcheng
District, Beijing 100730,
China; gaojm@pumch.ac.
cn
Received 9 August 2005
Accepted 6 February 2006
Published Online First
3 March 2006
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A

Background: Asthma is a complex polygenic disease in whichgene–environment interactions are
important. The gene encoding tumour necrosis factor alpha (TNFa) is one of several candidate loci for
asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism
of TNFa-308 gene promoter (substitution GRA, designated as TNF1 and TNF2) in relation to asthma
susceptibility in different populations. However, the results ofindividual studies have been inconsistent.
Methods: To address the inconsistent findings in studies of the association of the polymorphism of TNFa308 gene promoter with susceptibility to asthma, a systematic review was undertaken of the published
data and a meta-analysis was performed. The MEDLINE database was searched for case-control studies
published in English language journals from 1966to October 2005. Data were extracted using
standardised forms and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
Results: Fifteen eligible studies, comprising 2409 patients with asthma and 3266 controls, were included
in the meta-analysis. Using the random effects model, the pooled result showed that the TNF2 allele is
associated with overall susceptibility toasthma (OR 1.37, 95% CI 1.02 to 1.84, p = 0.04). The ORs for
asthma susceptibility in TNF2 homozygote individuals were significantly increased at 2.01 (95% CI 1.26 to
3.20, p = 0.009) and 1.51 (95% CI 1.02 to 2.22, p = 0.041) compared with TNF1 homozygotes and
TNF2/1 heterozygotes, respectively. In addition, the pooled OR for asthma risk in TNF2/1 heterozygotes
was also significantly higher thanthat in TNF1/1 homozygotes (OR 1.47, 95% CI 1.01 to 2.13,
p = 0.045).
Conclusions: The TNF2 allele confers a significant risk for developing asthma. A large scale case-control
study is needed to clarify the functional effect of the polymorphism of the TNFa gene in the pathogenesis of
asthma.

sthma is a complex disorder characterised by airway
inflammation that involves the interaction ofgenetic
and environmental factors. The genes predisposing to
asthma are likely to contain polymorphisms that modify
function. Tumour necrosis factor alpha (TNFa) is a potent
inflammatory cytokine whose encoding gene lies on the short
arm of chromosome 6.1 The TNFa gene may influence asthma
through modulation of non-specific inflammation.2 The
TNFa-308 promoter polymorphism is a bi-allelic G(named
TNF1 allele) to A (named TNF2 allele) polymorphism,3 and
the TNF2 allele is associated with increased levels of TNFa in
plasma and bronchoalveolar lavage fluid from asthmatic
airways.4 5 Thus, the central role of airway inflammation in
asthma and the increased levels of TNFa in asthmatic lungs
suggest that functional variants of the TNFa gene could be
important in this disease.
Anumber of studies have assessed the association between
the TNFa-308 promoter polymorphism and asthma in
different populations; however, the results are inconsistent
and inconclusive.6–25 Different methodologies have been used
but, in particular, most of the studies used a small sample
size and it is therefore not surprising that there has been a
lack of replication between the various...