Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function

Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin-alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2005-01, Vol.171 (2), p.171-176
Main Authors: Yang, Ian A, Holz, Olaf, Jörres, Rudolf A, Magnussen, Helgo, Barton, Sheila J, Rodríguez, Santiago, Cakebread, Julie A, Holloway, John W, Holgate, Stephen T
Format: Article
Language:English
Subjects:
Adult
Female
Genetic Predisposition to Disease
Haplotypes
Humans
Linkage Disequilibrium
Lung Diseases - epidemiology
Lung Diseases - etiology
Lung Diseases - genetics
Male
Ozone - adverse effects
Polymorphism, Genetic
Respiratory Function Tests
Tumor Necrosis Factor-alpha - genetics
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Summary:Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin-alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in 51 individuals who had undergone ozone challenge. Mean change in FEV1 with ozone challenge, as a percentage of baseline, was -3% in TNF -308G/A or A/A individuals, compared with -9% in G/G individuals (p = 0.024). When considering TNF haplotypes, the smallest change in FEV1 with ozone exposure was associated with the TNF haplotype comprising LTA +252G/TNF -1031T/TNF -308A/TNF -238G. This association remained statistically significant after correction for age, sex, disease, and ozone concentration (p = 0.047). SOD2 or GPX1 genotypes were not associated with lung function, and the TLR4 polymorphism was too infrequent to analyze. The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.200402-194OC