1. ¹Department of Pediatrics, Tsukuba Medical Center Hospital, Tsukuba, Japan
2. ²Laboratory of Genetics of Allergic Diseases, RIKEN SNP Research Center, Yokohama, Japan
3. ³Institute of Disability Sciences, Tsukuba, Japan
4. ⁴Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan
5. ⁵Department of Pediatrics, Tsukuba College of Technology, Tsukuba, Japan

Correspondence: Emiko Noguchi, Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan. E-mail: enoguchi@md.tsukuba.ac.jp

Received 24 January 2006; Accepted 30 April 2006; Published online 25 July 2006.

Abstract

Tumor necrosis factor (TNF) is a potent inflammatory cytokine that contributes to airway inflammation in asthma. Previous studies have reported that a G-to-A transition at position -308 (-308G/A, also referred to as TNF--308*1 and 308*2 respectively), is associated with asthma, but other studies have shown conflicting results. To investigate a possible association between the TNF-308G/A polymorphism and asthma, we performed transmission disequilibrium tests and a case-control study (family samples: 495 members in 165 Japanese trio families with one asthmatic child and both parents; case-control samples: 461 Japanese asthmatic children and 465 healthy controls). To increase the sample size and power, we performed a meta-analysis of all available relevant studies, including 2,477 asthmatics and 3,217 controls. We did not find a significant association between the TNF-308G/A polymorphism and childhood atopic asthma in two independent Japanese populations (P>0.05); however, meta-analysis revealed that the TNF-308G/A polymorphism was statistically significantly associated with asthma. The combined odds ratio with a fixed effects model and with a random effects for TNF-308A was 1.46 (95% confidence interval [CI], 1.27-1.68, P=0.0000001) and 1.46 (95% CI, 1.20-1.77, P=0.00014) respectively. Our data further support the importance of the TNF region in the development of asthma.