BETA-2 ADRENERGIC RECEPTOR POLYMORPHISMS AND ASTHMA

BETA-2 肾上腺素能受体多态性与哮喘

• 批准号: 2678088
• 负责人: AUGUSTO A LITONJUA
• 金额: $ 8.72万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-07 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2678088
• 关键词: asthma; beta adrenergic agent; beta adrenergic receptor; clinical research; genetic polymorphism; genetic susceptibility; human data; human population genetics; molecular pathology; respiratory disorder epidemiology; respiratory function

DESCRIPTION (Adapted from applicant's abstract) This proposal seeks to provide the opportunity for the Principal Investigator (PI) to gain knowledge and skills in molecular biology and genetic epidemiology, under the direct supervision of two highly qualified co-sponsors, to further enhance his potential to develop into an independent investigator. The PI is trained in clinical Pulmonary and Critical Care Medicine and has completed two years of a respiratory epidemiology fellowship, in addition to recently obtaining a M.P.H. degree. The first two years of this proposal will incorporate needed course-work, seminars, and hands-on laboratory experience in molecular biology and genetic techniques to enable the PI to undertake an intensive research experience in the latter three years of the proposal. The overall scientific goal of this proposal is to determine whether beta-2 adrenergic receptor polymorphisms are related to different asthma phenotypes. The case-control design, nested in a large, extensively phenotyped cohort will be utilized. The investigators propose to use the extensive information on airway reactivity, bronchodilator response, medication use, autonomic nervous system function, and markers of allergic and non-allergic inflammation to test the following hypotheses. They hypothesize that no B2AR polymorphism is a major causal factor of asthma. They hypothesize that the Arg16-Gly polymorphism is associated with increased airway responsiveness, depressed responsiveness to B-agonists, more frequent B-agonist and greater steroid use, greater autonomic dysfunction, greater degree of allergic and non-allergic inflammation. They hypothesize that the Gin27-Glu polymorphism is associated with decreased airway responsiveness, enhanced responsiveness to B-agonists, less frequent B-agonist and steroid use, less autonomic dysfunction, less allergic and nonallergic inflammation. The clinical benefit of this work is that if a particular genotype is associated with altered B-agonist response or resistance to B-adrenergic therapy, then alternative therapeutic approaches would be indicated in such individuals without having to go through a frustrating period of failure to respond to therapy. (End of Abstract)

描述 （改编自申请人的摘要）该提案旨在提供 首席研究员 (PI) 获得知识和技能的机会 在分子生物学和遗传流行病学的直接监督下 两位高素质的共同发起人，以进一步增强他的潜力 发展成为一名独立调查员。 PI接受过临床培训 肺科和重症监护医学，并已完成两年的学习 呼吸流行病学研究金，除了最近获得 公共卫生硕士程度。 该提案的前两年将纳入所需的 分子方面的课程作业、研讨会和实验室实践经验 生物学和遗传技术使 PI 能够进行强化研究 提案后三年的研究经历。 整体 该提案的科学目标是确定 beta-2 肾上腺素能是否 受体多态性与不同的哮喘表型相关。 这 病例对照设计，嵌套在一个大的、广泛表型的队列中 被利用。 研究人员建议利用广泛的信息 气道反应性、支气管扩张剂反应、药物使用、自主神经 神经系统功能以及过敏和非过敏标志物 炎症来检验以下假设。 他们假设没有 B2AR多态性是哮喘的主要致病因素。 他们假设 Arg16-Gly 多态性与气道扩张有关 反应性，对 B 激动剂的反应性降低，更频繁 B 激动剂和更多类固醇的使用，更大的自主神经功能障碍，更大的 过敏性和非过敏性炎症的程度。 他们假设 Gin27-Glu 多态性与气道反应性降低相关， 增强对 B 激动剂的反应性，减少使用 B 激动剂和类固醇的频率 使用后，植物神经功能紊乱较少，过敏性和非过敏性炎症较少。 这项工作的临床益处是，如果特定的基因型是 与 B 激动剂反应改变或对 B 肾上腺素能抗性相关 治疗，然后在这种情况下将表明替代治疗方法 个人不必经历失败的令人沮丧的时期 对治疗有反应。 （摘要完）