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

Yang, Ian A., Holz, Olaf, Jörres, Rudolf A., Magnussen, Helgo, Barton, Sheila J., Rodríguez, Santiago, Cakebread, Julie A., Holloway, John W. and Holgate, Stephen T. (2005) Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function. American Journal of Respiratory and Critical Care Medicine, 171 (2), 171-176. (doi:10.1164/rccm.200402-194OC).

Abstract

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.

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Contributors

Author: Sheila J. Barton

Author: John W. Holloway

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