Glutathione S-transferase Ml genotype [GSTM1] plus prenatal exposure to smoke as risk factors for pediatric asthma

ABSTRACT

Pediatric asthma is considered a complex multifactorial disease, with an obvious genetic predisposition and the possible involvement of noxious environmental factors. Glutathione S-transferase genes are known as risk factors predisposing to some environmentally induced diseases. This study has examined the hypothesis that glutathione S-transferase [GSTM1] genotype may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke. Genomic DNA samples isolated from 35 asthmatic children and 35 healthy children were amplified using the flanking GSTM1 primer set premixed with the internal set. Asthmatic children showed a significant high prevalence of the GSTM1-null genotype [odds ratio [OR] 2.2, 95% confidence interval [Cl] 1.4-3.4]. Among GSTM1-null children, in utero smoke exposure was associated with increased prevalence of asthma [OR 3.7, 95% Cl 1.9-7.3]. The intermediate electrophilic metabolites, arising in the first phase of detoxification of tobacco smoke, are not utilized by GST enzyme in asthmatic children. These intermediate metabolites may therefore attack cells and provoke oxidative stress, which contribute to the pathogenesis of asthma. Our findings indicate that there are important long-term effects of in utero smoke exposure in a genetically susceptible group of children [genetic environmental interaction]