GSTM1andGSTP1gene variants and the effect of air pollutants on lung function measures in South African children

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BackgroundSeveral 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.MethodsA 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).ResultsAmong 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.ConclusionAmong 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.

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