Gene-air pollution interactions in asthma.
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.
London
Stephanie J
SJ
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. London2@niehs.nih.gov
D001249:Asthma / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D010126:Ozone; D010641:Phenotype; D011110:Polymorphism, Genetic; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D010126:Ozone; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; C496556:GSTP1 protein, human