Ambient ozone modifies the effect of tumor necrosis factor G-308A on bronchitic symptoms among children with asthma.
BACKGROUND
Tumor necrosis factor (TNF)-alpha has a recognized role in respiratory pathophysiology. One genetic variant (G-308A) in the promoter region affecting the expression of this cytokine may contribute to airway inflammatory diseases, but the studies on bronchitic symptoms were still inconclusive. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the TNF-308 polymorphism with bronchitic symptoms may vary by ambient ozone exposure.


METHODS
We studied associations of TNF-308 genotype with bronchitic symptoms among asthmatic children in Children's Health Study. The association of TNF G-308A polymorphism with bronchitic symptoms was investigated and we also determined whether the associations vary with ambient ozone exposure.


RESULTS
Asthmatic children with TNF-308 GG genotype had a significantly reduced risk of bronchitic symptoms with low-ozone exposure (adjusted OR: 0.53; 95% CI: 0.31-0.91). The risk was not reduced in children living in high-ozone communities (adjusted OR: 1.42; 95% CI: 0.75-2.70). This difference in genotypic effects between low- and high-ozone environments was statistically significant among asthmatics (P for interaction = 0.01), but insignificant among nonasthmatic children.


CONCLUSIONS
Our findings suggest a role of gene-environmental interactions on the occurrence of bronchitic symptoms among children with asthma.
Lee
Y-L
YL
Institute of Preventive Medicine, National Taiwan University, Taipei, Taiwan.
McConnell
R
R
Berhane
K
K
Gilliland
F D
FD
D000293:Adolescent; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000235:genetics*; D002648:Child; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010126:Ozone / Q000633:toxicity*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha; D010126:Ozone