London Stephanie J
Epidemiology Branch and Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Proc Am Thorac Soc. 2007 Jul;4(3):217-20. doi: 10.1513/pats.200701-031AW.
Genetic and environmental factors interact to cause asthma. However, genetic studies have generally ignored environmental factors and environmental studies have generally ignored genetics. Thus, there are few examples from the literature of specific gene-environment interactions in relation to asthma. The clearest examples of genetic interactions for inhaled pollutants exist for endotoxin, environmental tobacco smoke, and ozone. Endotoxin-genetic interactions in asthma are the focus of two other manuscripts from this conference, so this review focuses on environmental tobacco smoke and ozone. In the sparse literature, there is evidence for the role of specific genes involved in oxidative stress, notably GSTM1 and TNF, in the respiratory responses to ozone and environmental tobacco smoke. There are few data on genes involved in innate immune pathways, which are crucial in response to endotoxin and may play a role in response to ozone and environmental tobacco smoke. Genes involved in oxidative stress may interact with both air pollutants and diet in relation to asthma phenotypes. Future directions to advance the field include whole genome association studies, better assessment of exposure and phenotypes, and consideration of joint interactions with diet and other co-factors that influence individual susceptibility.
遗传因素和环境因素相互作用导致哮喘。然而，遗传学研究通常忽略环境因素，而环境学研究通常忽略遗传学。因此，文献中关于哮喘的特定基因-环境相互作用的例子很少。吸入性污染物的遗传相互作用最明显的例子存在于内毒素、环境烟草烟雾和臭氧中。哮喘中的内毒素-遗传相互作用是本次会议另外两篇论文的重点，因此本综述聚焦于环境烟草烟雾和臭氧。在为数不多的文献中，有证据表明参与氧化应激的特定基因，尤其是谷胱甘肽硫转移酶M1（GSTM1）和肿瘤坏死因子（TNF），在对臭氧和环境烟草烟雾的呼吸道反应中发挥作用。关于参与固有免疫途径的基因的数据很少，这些基因在对内毒素的反应中至关重要，可能在对臭氧和环境烟草烟雾的反应中也发挥作用。参与氧化应激的基因可能在哮喘表型方面与空气污染物和饮食都存在相互作用。推动该领域发展的未来方向包括全基因组关联研究、更好地评估暴露和表型，以及考虑与饮食和其他影响个体易感性的共同因素的联合相互作用。
