Disclosure Statement: All authors declare no conflict of interest.
GSTM1 and GSTP1 gene variants and the effect of air pollutants on lung function measures in South African children†
Version of Record online: 6 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Industrial Medicine
Special Issue: Research Contributions from the United States International Training and Research in Environmental and Occupational Health Program: Part 1
Volume 55, Issue 12, pages 1078–1086, December 2012
How to Cite
Reddy, P., Naidoo, R. N., Robins, T. G., Mentz, G., Li, H., London, S. J. and Batterman, S. (2012), GSTM1 and GSTP1 gene variants and the effect of air pollutants on lung function measures in South African children. Am. J. Ind. Med., 55: 1078–1086. doi: 10.1002/ajim.22012
- Issue online: 7 NOV 2012
- Version of Record online: 6 JAN 2012
- Manuscript Accepted: 15 DEC 2011
- National Research Foundation (NRF), South Africa, supplemented by Durban University of Technology (DUT) KwaZulu-Natal, Durban, South Africa. Grant Number: 2068195 Thuthuka
- Ethekwini Municipality, KwaZulu Natal, Durban, South Africa. Grant Number: 1a-103—Health Study
- Intramural Research Program, National Institute of Environmental Health Sciences, NIH, USA. Grant Numbers: Z01 49019, Z01 ES025045
- US NIH Fogarty International Center. Grant Number: 2 D43 TW000812
- air pollutants;
- child respiratory health;
- gene–environment interaction
Several genes are associated with an increased susceptibility to asthma, which may be exacerbated by ambient air pollution. These genes include GSTM1 (glutathione-S-transferase M1 gene) and GSTP1 (glutathione-S-transferase P1 gene), which may modulate the response to epithelial oxidative changes caused by air pollutant exposure. This study evaluated fluctuations in the forced expiratory volume in one second (FEV1) in relation to lagged daily averages of ambient air pollutants (SO2, NO2, NO, and PM10) while considering genotype as an effect modifier.
A longitudinal cohort of 129 schoolchildren of African descent from Durban, South Africa was assessed. GSTM1 (null vs. present genotype) and GSTP1 (Ile105Val; AA AG/GG) genotypes were determined using standard techniques. SO2, NO2, NO, and PM10 were measured continuously over a year using validated methods. The outcome was intraday variability in FEV1. Data were collected daily over a 3-week period in each of four seasons (2004–2005).
Among the children tested, 27% had the GSTM1 null genotype and 81% carried the GSTP1 G allele. Approximately 26 out 104 children (25%) showed evidence of bronchial hyperreactivity, 13% reported having symptoms in keeping with persistent asthma, and a further 25% reported symptoms of mild intermittent asthma. PM10 and SO2 levels were moderately high relative to international guidelines. Neither GSTM1 nor GSTP1 genotypes alone were significantly associated with FEV1 intraday variability. In models not including genotype, FEV1 variability was statistically significantly associated only with NO2 for 5-day lags (% change in intraday variability in FEV1 per interquartile range = 1.59, CI 0.58, 2.61). The GSTP1 genotype modified the effect of 3 days prior 24-hr average PM10 and increased FEV1 variability. A similar pattern was observed for lagged 3 day SO2 exposure (P interaction < 0.05). Adverse effects of these pollutants were limited to individuals carrying the G allele for this polymorphism.
Among this indigenous South African children cohort, the GSTP1 genotype modified the effects of ambient exposures to PM10 and SO2 and lung function. A plausible mechanism for these observed effects is decreased capacity to mount an effective response to oxidative stress associated with the GSTP1 AG + GG genotype. Am. J. Ind. Med. 55:1078–1086, 2012. © 2012 Wiley Periodicals, Inc.