Glutathione S-Transferase M1 Genotype (GSTM1) Plus Prenatal Exposure to Smoke as Risk Factors for Pediatric Asthma

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 environ- mentally induced diseases. This study has examined the hypothesis that glu- tathione S-transferase (GSTM1) geno- type may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke. Genomic DNA samples isolated from 35 asth- matic children and 35 healthy children were amplified using the flanking GSTM1 primer set premixed with the internal set. Asthmatic children show- ed a significant high prevalence of the GSTM1-nu genotype (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4- 3.4). Among GSTM1-nu children, in utero smoke exposure was associated with increased prevalence of asthma (OR 3.7, 95% CI 1.9-7.3). The inter- mediate electrophilic metabolites, aris- ing 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 im- portant long-term effects of in utero smoke exposure in a genetically susc- ptible group of children (genetic- environmental interaction).