Pharmacogenetics of Beta2-Agonists in Asthma

Beta2 激动剂治疗哮喘的药物遗传学

• 批准号: 7884486
• 负责人: KATHRYN V BLAKE
• 金额: $ 12.36万
• 依托单位: NEMOURS CHILDREN'S CLINIC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884486
• 关键词: ADRB2 gene; Acute; Adenylyl Cyclase 9; Adrenal Cortex Hormones; Adrenergic Agonists; Adrenergic Receptor; Affect; African American; Aftercare; Agonist; Albuterol; American Lung Association; Asthma; Automobile Driving; Breathing; Bronchoconstriction; Bronchodilator Agents; Candidate Disease Gene; Caucasians; Caucasoid Race; Cessation of life; Chronic; Clinical; Clinical Research; Clinical Trials; Collection; Complex; Conflict (Psychology); Corticotropin-Releasing Hormone Receptors; DNA; Data; Databases; Disease; Drug Delivery Systems; Drug Prescriptions; Epidemiology; Failure; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Haplotypes; Incidence; Industry; Inflammatory; Investigator-Initiated Research; Lead; Life; Lung; Measures; Molecular Biology; Morbidity - disease rate; Obstruction; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacogenetics; Probability; Process; Publishing; Race; Research; Research Personnel; Research Project Grants; Role; Salmeterol; Scientist; Serotonin azidobenzamidine; Severity of illness; Single Nucleotide Polymorphism; Smooth Muscle; Stream; Symptoms; Testing; Training; Variant; abstracting; base; career; desensitization; genetic epidemiology; genetic variant; improved; interest; methacholine; mortality; prevent; programs; response; statistics

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)

描述（由申请人提供）：