Pharmacogenetics of Beta2-Agonists in Asthma

Beta2 激动剂治疗哮喘的药物遗传学

• 批准号: 7129241
• 负责人: KATHRYN V BLAKE
• 金额: $ 14.99万
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7129241
• 关键词: African American; adenylate cyclase; adolescence (12-20); adult human (21+); albuterol; asthma; beta adrenergic agent; beta adrenergic receptor; bronchodilators; caucasian American; clinical research; corticotropin releasing factor; drug resistance; drug screening /evaluation; genetic screening; human genetic material tag; human subject; human therapy evaluation; human tissue; methacholine; patient oriented research; pharmacogenetics; racial /ethnic difference; respiratory disorder chemotherapy; respiratory pharmacology; single nucleotide polymorphism

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）： 该候选人是一位高级研究科学家，15 年来一直成功指导行业赞助的哮喘临床试验项目。她希望将自己的职业生涯从行业资助的研究转变为研究者发起的哮喘药物遗传学研究，并成功争取资金。她的研究兴趣是确定患者对哮喘药物反应差异的遗传原因。为了实现她的职业目标，她将接受分子生物学、遗传学、流行病学、统计学和资助方面的课程和培训。她将得到哮喘药物遗传学、统计遗传学、肺部流行病学、药物靶点药物遗传学和分子生物学领域专家科学家的指导。她将完成一个有两个具体目标的研究项目。具体目标 1：确定白种人和非裔美国人的 p2 肾上腺素受体 (P2 AR) 通路多态性与沙丁胺醇支气管扩张剂反应之间的关联；具体目标 2：确定选定的 p2 AR 多态性在 p2 激动剂促进白种人和非裔美国人接受沙美特罗治疗后脱敏中的作用。具体目标 1 将通过对来自美国肺脏协会哮喘临床研究中心网络试验期间获得的现有 DNA 集合中的 p2 AR 途径候选基因的 30 多个单核苷酸多态性进行基因分型来实现，并分析遗传变异与支气管扩张剂对沙丁胺醇的反应之间的关联。具体目标 2 将在一项临床研究中完成，以确定哪些具有特定 p2 AR 双倍型的患者对沙美特罗引起的脱敏敏感；脱敏效果将通过乙酰甲胆碱激发试验和支气管扩张剂对沙丁胺醇的反应来测量。该提案将为研究者发起的哮喘药物遗传学研究做好准备，其结果可能允许临床医生使用药物遗传学数据来选择合适的短效和长效 p2 激动剂治疗哮喘。 （摘要完）