An association between asthma and TNF-308G/A polymorphism: meta-analysis.
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.
Aoki
Takeshi
T
Department of Pediatrics, Tsukuba Medical Center Hospital, Tsukuba, Japan.
Hirota
Tomomitsu
T
Laboratory of Genetics of Allergic Diseases, RIKEN SNP Research Center, Yokohama, Japan.
Tamari
Mayumi
M
Laboratory of Genetics of Allergic Diseases, RIKEN SNP Research Center, Yokohama, Japan.
Ichikawa
Kunio
K
Department of Pediatrics, Tsukuba Medical Center Hospital, Tsukuba, Japan.
Takeda
Kazunori
K
Institute of Disability Sciences, Tsukuba, Japan.
Arinami
Tadao
T
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8577, Japan.
Shibasaki
Masanao
M
Department of Pediatrics, Tsukuba College of Technology, Tsukuba, Japan.
Noguchi
Emiko
E
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8577, Japan. enoguchi@md.tsukuba.ac.jp.
D000328:Adult; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha