Association between polymorphism of tumour necrosis factor α-308 gene promoter and asthma: a meta-analysis
- 1Department of Respiratory Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
- 2Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China
- 3Hypertension and Atherosclerosis Section, Boston University School of Medicine, Boston, MA 02118, USA
- 4Asthma and Allergy Research Institute and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, WA 6009, Australia
- 5Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
- Correspondence to:
Dr J Gao
Department of Respiratory Diseases, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China; gaojm{at}pumch.ac.cn
- Received 9 August 2005
- Accepted 6 February 2006
- Published Online First 3 March 2006
Abstract
Background: Asthma is a complex polygenic disease in which gene–environment interactions are important. The gene encoding tumour necrosis factor alpha (TNFα) is one of several candidate loci for asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism of TNFα-308 gene promoter (substitution G→A, designated as TNF1 and TNF2) in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent.
Methods: To address the inconsistent findings in studies of the association of the polymorphism of TNFα-308 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 1966 to 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 to asthma (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 than that 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 TNFα gene in the pathogenesis of asthma.
Footnotes
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Published Online First 3 March 2006
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This work was in part funded by a grant from National Natural Sciences Foundation of China (No 30470767 to Jinming Gao). Jinming Gao is also supported by the Youth Fellowship from Peking Union Medical College Hospital. Philip J Thompson’s involvement in this research was supported by the CRC for Asthma and Airways.
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The authors declare no financial conflict in the preparation of this manuscript.
