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Pharmacogenomic approaches to drug metabolism in American Indian/Alaska Native People

美洲印第安人/阿拉斯加原住民药物代谢的药物基因组学方法

基本信息

批准号：
10603294
负责人：
Katrina G Claw
金额：
$ 29.41万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10603294
关键词：
Alaska Alaska Native American Indians Biological Assay Cataloging Clinical Communities Drug Targeting Ethics Ethnic group Excretory function Foundations Gene Frequency Genetic Variation Genetic study Genomics Genotype Geography Goals Guidelines Individual Knowledge Metabolism Modeling Native-Born Outcome Pharmaceutical Preparations Pharmacogenetics Pharmacogenomics Pharmacology Phenotype Population Population Heterogeneity Race Research Research Project Grants Treatment Protocols Underrepresented Populations Variant Work absorption clinical application community engaged research community engagement drug efficacy drug metabolism genomic variation improved in silico in vivo individualized medicine inter-individual variation intertribal marginalized population medication safety novel personalized medicine pharmacogenetic testing response

项目摘要

From original submission, has not changed. Summary Pharmacogenetic testing is expected to enhance drug safety and efficacy while improving clinical outcomes by tailoring treatment regimens to the individual. Key to maximizing benefits of this approach will be comprehensive characterization of genetic variation that modulates drug absorption, distribution, metabolism and excretion, drug target interaction and pharmacological response across populations. Significant advances in cataloguing pharmacogenomic profiles from major populations of the world have aided clinical applications but have largely excluded historically marginalized populations and small, geographically isolated populations, including American Indian and Alaska Native (AIAN) people. These populations continue to be underrepresented in genomic research for a variety of reasons: lack of community engagement, historical mistrust, and geographical remoteness. Recent genetic studies by the Northwest Alaska Pharmacogenetic Research Network (NWA-PGRN)—a center with multiple institutional and tribal partners—have shown that AIAN people carry variants in pharmacogenes that are both novel and common, have allele frequencies of known variants that are different than other ethnic or racial groups, and display high inter-tribal variability as well. To broaden this research, we propose to leverage the lessons learned and build on research from the NWA-PGRN to understand inter-individual variation in drug responses and provide novel indicators and guidelines for implementing personalized medicine in AIAN communities. Our overall goal is to fill this knowledge gap through characterizing genomic variation of pharmacogenes in a wide range of AIAN populations using an ethical and community-engaged framework that focuses on developing and deepening research partnerships with AIAN communities. We also seek to investigate the relationships between genotype-phenotype of novel variants using in silico prediction and in vivo functional assays. This work will create a general model for genomic research that engages communities in the research plan throughout the research project (from start to completion and beyond) and will serve as a foundational way to shift the research framework in genomics.

从最初提交，没有改变。