GSTM1 and GSTP1 gene variants and the effect of air pollutants on lung function measures in South African children

Background: 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 (FEV(1)) in relation to lagged daily averages of ambient air pollutants (SO(2), NO(2), NO, and PM(10)) while considering genotype as an effect modifier.

Methods: 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. SO(2), NO(2), NO, and PM(10) were measured continuously over a year using validated methods. The outcome was intraday variability in FEV(1) . Data were collected daily over a 3-week period in each of four seasons (2004-2005).

Results: 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. PM(10) and SO(2) levels were moderately high relative to international guidelines. Neither GSTM1 nor GSTP1 genotypes alone were significantly associated with FEV(1) intraday variability. In models not including genotype, FEV(1) variability was statistically significantly associated only with NO(2) 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 PM(10) and increased FEV(1) variability. A similar pattern was observed for lagged 3 day SO(2) exposure (P interaction < 0.05). Adverse effects of these pollutants were limited to individuals carrying the G allele for this polymorphism.

Conclusion: Among this indigenous South African children cohort, the GSTP1 genotype modified the effects of ambient exposures to PM(10) and SO(2) 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.