Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children
Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children
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DOI：
10.1164/rccm.2112064
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发表时间：
2002-08-15
影响因子：
24.7
通讯作者：
Peters, JM
中科院分区：
文献类型：
--
作者：
Gilliland, FD;Li, YF;Peters, JM
儿童哮喘患病率的上升表明环境因素在这一不断演变的流行病的病因学中发挥了作用；然而，遗传因素也会影响哮喘的发生。谷胱甘肽 S-转移酶 (GST) M1 可能在接触烟草烟雾的哮喘和喘息发生中发挥作用，因为它在涉及哮喘发病机制的途径中发挥作用，例如外源代谢和抗氧化防御。 GSTM1 基因型、母亲怀孕期间吸烟以及儿童环境烟草烟雾 (ETS) 暴露对哮喘和喘息的影响对南加州 12 个社区的 4、7 和 10 年级教室的 2,950 名儿童进行了调查。子宫内母亲吸烟对哮喘和喘息发生的影响主要限于 GSTM1 无效基因型的儿童。在 GSTM1 缺失儿童中，子宫内暴露与早发哮喘（比值比 [OR] 1.6，95% 置信区间 [CI] 1.0-2.5）、有当前症状的哮喘（OR 1.7，95% Cl 1.1-2.8）、持续性哮喘（OR 1.6，95% Cl 1.1-2.4）、终生喘息史（OR 1.8, 95% Cl 1.3-2.5）、运动时喘息（OR 2.1，95% Cl 1.3-3.3）、需要药物治疗的喘息（OR 2.2，95% Cl 1.4-3.4）以及过去一年内急诊室就诊（OR 3.7，95% Cl 1.9-7.3）。在具有 GSTM1 (+) 基因型的儿童中，子宫内暴露与哮喘或喘息无关。我们的研究结果表明，子宫内暴露会对遗传易感儿童群体产生重要的长期影响。
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% Cl 1.1-2.8), persistent asthma (OR 1.6, 95% Cl 1.1-2.4), lifetime history of wheezing (OR 1.8, 95% Cl 1.3-2.5), wheezing with exercise (OR 2.1, 95% Cl 1.3-3.3), wheezing requiring medication (OR 2.2, 95% Cl 1.4-3.4), and emergency room visits in the past year (OR 3.7, 95% Cl 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.