Pharmacogenetics in Rural and Underserved Populations

描述（由申请人提供）：基因检测提供了确定药物处置和反应的个体间变异来源的机会，其目标是个体化治疗（药物选择和剂量）并改善患者和公众健康结果。少数药物遗传学测试已经在临床使用，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，但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。居住在农村地区的阿拉斯加原住民和美洲印第安人（AI/AN）社区的信息差距尤其明显；解决这些差距需要关注科学、保健服务和文化问题。我们缺乏对美国土著人口中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，人们对土著社区基因研究的潜在文化障碍知之甚少，这些文化障碍可能会推迟这项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种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人群中建立一个新的药物遗传学中心。该中心将与阿拉斯加州安克雷奇、阿拉斯加育空-库斯科金三角洲和蒙大拿州西北部的土著社区，以及这些地区和华盛顿州农村地区的农村医疗服务提供者合作，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对药物遗传学的看法；在AI/AN和农村社区开展与基因变异和对华法林、他莫昔芬和他克莫司治疗反应相关的基础研究；评估一个土著社区中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。

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.