cDNA Microarrays for Pharmacogenomic Analysis of Cystic Fibrosis

Cystic fibrosis (CF) is a single-gene disorder with a complex phenotype, in which multiple organs are affected. The pulmonary complications of CF, including mucous plugging and chronic bacterial infection of the lung, represent the major cause of morbidity and mortality (1 ). It has long been suggested that mutations in CFTR, localized to the apical membrane of airway epithelia, lead to abnormalities in the fluid lining the airway surface. Accumulating evidence suggests that the inflammatory response in the CF lung may be excessive. However, it is not clear to what extent this reflects unusual persistence of stimulation of this response by bacteria or other pathogens, vs to what extent defects in CFTR might by themselves stimulate or cause dysregulation of inflammatory responses. Changes in the multigene patterns of expression can provide clues about regulatory mechanisms and broader cellular functions and biochemical pathways. In the context of cystic fibrosis disease and treatment, the knowledge gained from these types of measurements can help determine the causes and consequences of disease, how drugs and drug candidates work in cells and organisms, and what gene products might have therapeutic uses themselves or may be appropriate targets for therapeutic intervention.