Pharmacogenetics in Rural and Underserved Populations

农村和服务不足人群的药物遗传学

• 批准号: 8110046
• 负责人: WYLIE G. BURKE
• 金额: $ 200.73万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8110046
• 关键词: Address; Affect; Alaska; Alaska Native; American Indian and Alaska Native; American Indians; Anticoagulation; Applications Grants; Attention; Biological; Blood; Blood Coagulation Factor; Breast Cancer Treatment; CYP2C9 gene; CYP2D6 gene; CYP3A4 gene; CYP3A5 gene; Caring; Case-Control Studies; Cells; Chinese Hamster Ovary Cell; Chronic; Clinic; Clinical; Coagulation Process; Collaborations; Communities; Consultations; Consumption; Coupled; DNA Resequencing; Data; Diet; Dose; Drug Kinetics; Engineering; Enrollment; Ensure; Environment; Enzymes; Eskimo Population; Ethnic group; Event; Factor IX; Fatty Acids; Foundations; Future; Gene Frequency; Gene Mutation; Genes; Genetic; Genetic Polymorphism; Genetic Research; Genetic Variation; Genetic screening method; Genotype; Geographic Locations; Goals; Health; Health Personnel; Health Services; Healthcare; Hemorrhage; Hepatocyte; Human; Idaho; In Vitro; Indigenous; Individual; Information Technology; Institutes; Intake; Investigation; Kidney Transplantation; Knowledge; Life; Link; Liver; Liver Microsomes; Location; Measures; Medical; Messenger RNA; Metabolic; Metabolism; Mind; Monitor; Montana; Mutation; Native-Born; Outcome; Pacific Northwest; Participant; Patients; Perception; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pharmacotherapy; Phenotype; Plasma; Polyunsaturated Fatty Acids; Population; Population Study; Primary Health Care; Principal Investigator; Proteins; Prothrombin; Provider; Public Health; Qualitative Research; Randomized Clinical Trials; Recommendation; Reporting; Research; Research Infrastructure; Research Methodology; Research Personnel; Resources; Risk; Rural; Rural Community; Rural Health; Rural Population; Safety; Salish and Kootenai Tribes; Services; Site; Source; System; Tacrolimus; Tamoxifen; Testing; Therapeutic; Treatment Efficacy; Uncertainty; Underserved Population; Universities; Variant; Vitamin K; Warfarin; Washington; Work; Wyoming; Yukon Territory; Yup' ik; acarboxy prothrombin; base; clinical practice; community based participatory research; community living; design; enzyme activity; gene environment interaction; improved; in vivo; indexing; interest; novel; pharmacogenetic testing; programs; prospective; racial and ethnic; research clinical testing; research study; response; tertiary care; translational health science; uptake

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.

描述(由申请人提供)：基因测试提供了确定药物处置和反应中个体间差异的来源的机会，目的是个体化治疗(药物选择和剂量)并改善患者和公共健康结果。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。尽管有这样的前景，但大多数研究都是在资源密集型的三级护理中心进行的，它们与农村卫生保健实践的相关性尚不清楚。对于居住在农村地区的阿拉斯加原住民和美国印第安人(AI/AN)社区来说，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。我们缺乏关于美国土著人口中相关遗传和环境变异的知识，限制了我们为这些群体提供药物遗传测试服务的设计和实施的能力。此外，人们对土著社区内潜在的遗传研究文化障碍知之甚少，这些障碍可能会推迟这项研究议程或限制人们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育空-库斯科金三角洲的土著社区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、生物学知识和医疗基础设施，以适当回应与药物遗传学相关的国家建议或任务。我们中心将利用以社区为基础的参与性研究方法来评估社区和临床对药物遗传学的观点；在人工智能/AN和农村社区进行与华法林、他莫昔芬和他克莫司治疗的遗传变异和反应相关的基础研究；评估一个土著社区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、多文化的赠款申请中提出的具体目标，可以通过解决主要的科学知识差距和潜在的文化/结构障碍来解决药物遗传研究及其临床测试的潜在文化/结构障碍，从而提高我们对药物遗传多样性的理解，并增强美洲印第安人和阿拉斯加土著人民的药物安全性/有效性。