Pharmacogenetics in Rural and Underserved Populations

描述（由申请人提供）：基因检测提供了一个机会，以确定药物处置和反应的个体间变异性的来源，其目标是个性化治疗（药物选择和剂量），并改善患者和公共卫生结果。少数药物遗传学测试已经在临床上使用，其他有希望的例子正在出现，包括提高华法林，他莫昔芬和他克莫司治疗安全性的测试。尽管有这样的希望，大多数研究都是在资源密集型的三级保健中心进行的，它们与农村卫生保健实践的相关性尚不清楚。生活在农村地区的阿拉斯加土著和美洲印第安人社区的信息差距尤其明显;解决这些差距需要关注科学、卫生服务和文化问题。我们缺乏对美国土著人群相关遗传和环境变异的了解，限制了我们为这些群体设计和实施药物遗传学检测服务的能力。此外，人们对土著社区内遗传研究的潜在文化障碍知之甚少，这些障碍可能会推迟这一研究议程或限制对药物遗传学的接受，也不知道最佳实施这一临床方法所需的资源。考虑到这些不确定性和知识差距，我们建议在农村和服务不足的人群中建立一个新的药物遗传学中心。该中心将与安克雷奇和阿拉斯加的育空-库斯科金三角洲以及蒙大拿州西北部的土著社区合作，并与这些地区和华盛顿农村的农村提供者合作，以确保有足够的社区理解，生物知识和医疗基础设施，以适当地响应与药物遗传学相关的国家建议或任务。我们的中心将利用社区参与式研究方法来评估社区和临床药物遗传学的观点;在AI/AN和农村社区进行与遗传变异和对华法林，他莫昔芬和他克莫司治疗的反应相关的基础研究;在一个土著社区评估与凝血因子相关的基因-环境相互作用;并为将AI/AN社区农村实践与药物遗传学研究人员联系起来的研究基础设施奠定基础。 相关性：完成这项多学科、多文化资助申请中提出的具体目标可以提高我们对药物遗传学变异性的理解，并通过解决药物遗传学研究及其临床试验的主要科学知识差距和潜在文化/结构障碍，提高美洲印第安人和阿拉斯加原住民的药物安全性/有效性。

DESCRIPTION (provided by applicant): Genetic testing offers the opportunity to identify sources of inter-individual variability in drug disposition and response, with the goal of individualizing therapy (drug selection and dose) and improving patient and public health outcomes. A small number of pharmacogenetic tests are already in clinical use, and other promising examples are emerging, including tests to improve the safety of warfarin, tamoxifen and tacrolimus therapy. Despite this promise, most studies have been undertaken in resource-intensive, tertiary care centers and their relevance for rural health care practice is unknown. Information gaps are especially notable for Alaska Native and American Indian (AI/AN) communities living in rural locations; addressing these gaps requires attention to scientific, health service and cultural issues. We lack knowledge about relevant genetic and environmental variation within indigenous populations of the US, limiting our ability to inform the design and implementation of pharmacogenetic testing services for these groups. In addition, little is known about potential cultural barriers to genetic research within indigenous communities that might delay this research agenda or limit receptiveness to pharmacogenetics, or about the resources that would be needed for optimal implementation of this clinical approach. With these uncertainties and knowledge gaps in mind, we propose to create a new Center on Pharmacogenetics in Rural and Underserved Populations. This Center will work in partnership with indigenous communities in Anchorage and the Yukon-Kuskowkim delta in Alaska and in northwestern Montana, and with rural providers in these locations and in rural Washington, to ensure that there is adequate community understanding, biological knowledge, and medical infrastructure to respond appropriately to national recommendations or mandates related to pharmacogenetics. Our Center will utilize community-based participatory research methods to evaluate community and clinical perspectives on pharmacogenetics; pursue foundational research in AI/AN and rural communities related to genetic variation and response to warfarin, tamoxifen and tacrolimus therapy; evaluate gene-environment interactions related to coagulation factors in one indigenous community; and lay the groundwork for a research infrastructure linking AI/AN communities rural practices to pharmacogenetics researchers. RELEVANCE: Completion of the specific aims proposed in this multi-disciplinary, multi-cultural grant application could improve our understanding of pharmacogenetic variability and enhance drug safety/efficacy in American Indian and Alaska Native peoples, by addressing major scientific knowledge gaps and potential cultural/structural barriers to pharmacogenetic research and its clinical testing.