Pharmacogenetics of Beta2-Agonists in Asthma

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DESCRIPTION (provided by applicant): The candidate is a senior research scientist who has directed a successful industry sponsored asthma clinical trials program for 15 years. She desires to transition her career from industry sponsored research to investigator-initiated research in asthma pharmacogenetics and successfully compete for funding. Her research interest is to determine the genetic causes for inter-patient differences in the response to asthma drugs. To achieve her career goal, she will have coursework and training in molecular biology, genetics, epidemiology, statistics, and grantsmanship. She will be guided by expert scientists in asthma pharmacogenetics, statistical genetics, pulmonary epidemiology, drug target pharmacogenetics, and molecular biology. She will complete a research project with 2 specific aims. Specific Aim 1: to determine associations between p2 adrenergic receptor (P2 AR) pathway polymorphisms and bronchodilator response to albuterol in Caucasians and African Americans; Specific Aim 2: to determine the role of selected p2 AR polymorphisms in p2-agonist promoted desensitization following treatment with salmeterol in Caucasians and African Americans. Specific Aim 1 will be accomplished by genotyping over 30 single nucleotide polymorphisms on p2 AR pathway candidate genes from an extant collection of DNA obtained during an American Lung Association Asthma Clinical Research Centers network trial and analyze associations between the genetic variants and bronchodilator response to albuterol. Specific Aim 2 will be accomplished in a clinical study to determine which patients with specific p2 AR diplotypes are susceptible to desensitization caused by salmeterol; desensitization effects will be measured by methacholine challenge testing and bronchodilator response to albuterol. This proposal will prepare the candidate for investigator initiated research in asthma pharmacogenetics and results may allow clinicians to use pharmacogenetic data to select appropriate short- and long-acting p2agonist therapy in asthma. (End of Abstract)