The Egyptian Journal of Medical Human Genetics, Vol. 6, No. 2, Nov. 2005. 183 Glutathione S-Transferase M1 Genotype (GSTM1) Plus Prenatal Exposure to Smoke as Risk Factors for Pediatric Asthma Maged A.A.F. Ibrahim,* Malak A. Shaheen,* Nasser A. Elhawary,** Rasha A. Abdel Fattah* * Pediatrics Department, Faculty of Medicine, and Medical Genetic Center, **AinShams University, Cairo 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 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-null genotype (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4- 3.4). Among GSTM1-null 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). Introduction: Asthma affects nearly 14 million people worldwide and has been stea- dily increasing in frequency for the past 50 years. (1) Although environme- ntal factors clearly influence the onset, progression, and severity of this dise- ase, family and twin studies indicate that genetic variation also influences susceptibility. (2,3) Although a rapid rise in childhood asthma prevalence sug- gests a role for environmental factors in the aetiology of this evolving epide- mic, it is logistic that genetics also in- fluence the occurrence of asthma. (4-6) The evidence that both genes and en- vironment play etiologic roles sugges- ts that the increase in asthma occur- rence is likely to involve changes in specific exposures among the popula- tion of genetically susceptible individu- als. (7,8) The full spectrum of exposures and susceptibility genes involved in the pathogenesis of asthma and wheezing have yet to be establish- ed (6,9) Tobacco smoke is an exposure