ASTHMA

Association between polymorphism of tumour necrosis factor -308 gene promoter and asthma: a meta-analysis

J Gao¹, G Shan², B Sun³, P J Thompson⁴, X Gao⁵

¹ Department of Respiratory Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
² Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100005, China
³ Hypertension and Atherosclerosis Section, Boston University School of Medicine, Boston, MA 02118, USA
⁴ Asthma and Allergy Research Institute and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, WA 6009, Australia
⁵ Department 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

Background: Asthma is a complex polygenic disease in which gene–environment interactions are important. The gene encoding tumour necrosis factor alpha (TNF) is one of several candidate loci for asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism of TNF-308 gene promoter (substitution GA, 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 TNF-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 TNF gene in the pathogenesis of asthma.

Abbreviations: TNF, tumour necrosis factor alpha

Keywords: asthma; genetics; tumour necrosis factor; polymorphism; meta-analysis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Morjaria, J B, Chauhan, A J, Babu, K S, Polosa, R, Davies, D E, Holgate, S T (2008). The role of a soluble TNF{alpha} receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 63: 584-591 [Abstract] [Full Text]  
• DeMeo, D. L., Campbell, E. J., Barker, A. F., Brantly, M. L., Eden, E., McElvaney, N. G., Rennard, S. I., Sandhaus, R. A., Stocks, J. M., Stoller, J. K., Strange, C., Turino, G., Silverman, E. K. (2008). IL10 Polymorphisms Are Associated with Airflow Obstruction in Severe {alpha}1-Antitrypsin Deficiency. Am. J. Respir. Cell Mol. Bio. 38: 114-120 [Abstract] [Full Text]  
• Beleza-Meireles, A., Kockum, I., Lundberg, F., Soderhall, C., Nordenskjold, A. (2007). Risk Factors for Hypospadias in the Estrogen Receptor 2 Gene. J. Clin. Endocrinol. Metab. 92: 3712-3718 [Abstract] [Full Text]  
• Park, H.-W., Shin, E.-S., Lee, J.-E., Kwon, H.-S., Chun, E., Kim, S.-S., Chang, Y.-S., Kim, Y.-K., Min, K.-U., Kim, Y.-Y., Cho, S.-H. (2007). Multilocus analysis of atopy in Korean children using multifactor-dimensionality reduction. Thorax 62: 265-269 [Abstract] [Full Text]  
• Sharma, S., Sharma, A., Kumar, S., Sharma, S. K., Ghosh, B. (2006). Association of TNF Haplotypes with Asthma, Serum IgE Levels, and Correlation with Serum TNF-{alpha} Levels. Am. J. Respir. Cell Mol. Bio. 35: 488-495 [Abstract] [Full Text]  
• Krayenbuehl, P.-A., Maly, F. E., Hersberger, M., Wiesli, P., Himmelmann, A., Eid, K., Greminger, P., Vetter, W., Schulthess, G. (2006). Tumor Necrosis Factor-{alpha} -308G>A Allelic Variant Modulates Iron Accumulation in Patients with Hereditary Hemochromatosis. Clin. Chem. 52: 1552-1558 [Abstract] [Full Text]