Pharmacogenetics in Rural and Underserved Populations

农村和服务不足人群的药物遗传学

基本信息

批准号：
8521321
负责人：
WYLIE G. BURKE
金额：
$ 179.78万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/8521321
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&apos 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

项目摘要

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）：基因检测提供了确定药物处置和反应中个体变异源的机会，其目的是个性化治疗（药物选择和剂量），并改善患者和公共健康结果。少量的药物遗传学测试已经在临床上进行，其他有希望的例子正在出现，包括改善华法林，他莫昔芬和他克莫司疗法的安全性测试。尽管有这样的承诺，但大多数研究还是在资源密集型，高等教育中心及其与农村医疗保健实践的相关性进行的研究尚不清楚。对于居住在农村地区的阿拉斯加土著印第安人和美洲印第安人（AI/AN）社区而言，信息差距尤其值得注意；解决这些差距需要注意科学，卫生服务和文化问题。我们缺乏有关美国土著人口中相关的遗传和环境变异的知识，从而限制了我们为这些群体的药物遗传学测试服务的设计和实施的能力。此外，对土著社区内遗传研究的潜在文化障碍知之甚少，这些文化障碍可能会延迟该研究议程或限制对药物遗传学的接受，或者限制了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的人群中建立一个关于药物遗传学的新中心。该中心将与阿拉斯加和蒙大拿州西北部的安克雷奇和育空地区的土著社区以及在这些地点和华盛顿乡村的农村提供商合作，以确保有足够的社区知识，生物学知识和医学性与全国性的建议相关，以确保有足够的社区认识，以确保有足够的社区知识，以确保有适当的社区认识，以确保适当地授权制药。我们的中心将利用基于社区的参与研究方法来评估社区和有关药物遗传学的临床观点；在AI/AN和农村社区中进行与遗传变异以及对华法林，他莫昔芬和他克莫里木马疗法有关的基础研究；评估一个土著社区中与凝血因子有关的基因环境相互作用；并为将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了基础。相关性：完成此多学科的多元文化赠款应用中提出的具体目的可以提高我们对药物遗传学可变性的理解，并通过解决对药物遗传学研究及其临床测试的主要科学知识差距以及潜在的文化/结构障碍，从而提高美洲印第安人和阿拉斯加土著人民的药物安全/功效。