An association between asthma and TNF-308G/A polymorphism: meta-analysis

J Hum Genet. 2006;51(8):677-685. doi: 10.1007/s10038-006-0007-3. Epub 2006 Jul 25.


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-alpha-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.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Asthma / genetics*
  • Case-Control Studies
  • Child
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Japan
  • Male
  • Odds Ratio
  • Polymorphism, Genetic / genetics*
  • Sensitivity and Specificity
  • Tumor Necrosis Factor-alpha / genetics*


  • TNF protein, human
  • Tumor Necrosis Factor-alpha