The Genetics of Environmental Airway Disease

Duke University, Durham NC

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Abstract

DESCRIPTION (provided by applicant): Asthma is a disease of great clinical importance and increasing prevalence. Its pathogenesis has not been well-understood because of the phenotypic heterogeneity of the disease, the heterogeneity of underlying biology, and the critical role played by environmental exposures. It is conceivable that polymorphisms of genes expressed by the airway epithelia in asthmatics following specific airway challenges predispose individuals to the development of asthma. To investigate this hypothesis, human subjects with well characterized allergy, mild asthma, both or neither will be recruited and challenged bronchoscopically with airway instillation of saline, house dust mite antigen, and lipopolysaccharide. Post-challenge inflammatory and epithelial cells will be collected from these patients and analyzed, with particular focus on gene expression array data. Candidate asthma susceptibility genes will be identified through gene expression, and gene association studies will be performed by comparing our sample population to other asthma populations. Candidate genes will then by analyzed for sequence polymorphisms in asthmatics. This model of airway disease is a potentially very powerful tool to elucidate important gene-environment interactions.