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Effects of Glutathione S-Transferase M1, Maternal Smoking during Pregnancy, and Environmental Tobacco Smoke on Asthma and Wheezing in Children

University of Southern California Keck School of Medicine, Department of Preventive Medicine, Los Angeles, California

Correspondence and requests for reprints should be addressed to Frank Gilliland, M.D., Ph.D., Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033. E-mail: gillilan{at}hsc.usc.edu

The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functions in pathways involved in asthma pathogenesis such as xenobiotic metabolism and antioxidant defenses. Effects of GSTM1 genotype, maternal smoking during pregnancy, and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 2,950 children enrolled in 4th, 7th, and 10th grade classrooms in 12 Southern California communities. The effects of in utero exposure to maternal smoking on asthma and wheezing occurrence were largely restricted to children with GSTM1 null genotype. Among GSTM1 null children, in utero exposure was associated with increased prevalence of early onset asthma (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0–2.5), asthma with current symptoms (OR 1.7, 95% CI 1.1–2.8), persistent asthma (OR 1.6, 95% CI 1.1–2.4), lifetime history of wheezing (OR 1.8, 95% CI 1.3–2.5), wheezing with exercise (OR 2.1, 95% CI 1.3–3.3), wheezing requiring medication (OR 2.2, 95% CI 1.4–3.4), and emergency room visits in the past year (OR 3.7, 95% CI 1.9–7.3). Among children with GSTM1 (+) genotype, in utero exposure was not associated with asthma or wheezing. Our findings indicate that there are important long-term effects of in utero exposure in a genetically susceptible group of children.

Key Words: In utero exposure • tobacco smoke • GSTM1 • asthma • wheeze • children

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