ArticlePharmacogenetics and genomics2015
Variation in genes controlling warfarin disposition and response in American Indian and Alaska Native people: CYP2C9, VKORC1, CYP4F2, CYP4F11, GGCX.
Article in Pharmacogenetics and genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations.Molecular genetics & genomic medicine · 2024Pooled it
- Structural disruption of VKORC1 by resistance mutations reveals a conserved hydrophobic pattern essential for warfarin binding: insights from molecular dynamics analyses.Molecular diversity · 2026Article
- Use of Cognitive Interviews in the Development of a Survey Assessing American Indian and Alaska Native Adult Perspectives on Genetics and Biological Specimens.International journal of environmental research and public health · 2024Article
- Implementing community-engaged pharmacogenomics in Indigenous communities.Nature communications · 2024Article
- Characterization of Gla proteoforms and non-Gla peptides of gamma carboxylated proteins: Application to quantification of prothrombin proteoforms in human plasma.Analytica chimica acta · 2023Article
- Genomics and inclusion of Indigenous peoples in high income countries.Human genetics · 2023Review
- The Value of Pharmacogenomics for White and Indigenous Americans after Kidney Transplantation.Pharmacy (Basel, Switzerland) · 2023Article
- One Rare Warfarin Resistance Case and Possible Mechanism Exploration.Pharmacogenomics and personalized medicine · 2023Article
- Tribal Deliberations about Precision Medicine Research: Addressing Diversity and Inequity in Democratic Deliberation Design and Evaluation.Journal of empirical research on human research ethics : JERHRE · 2022Article
- Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.Clinical and translational science · 2021Observational
- In Vivo Functional Effects ofDrug metabolism and disposition: the biological fate of chemicals · 2021Article
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Heterologous Expression and Functional Characterization of Novel CYP2C9 Variants Identified in the Alaska Native People.The Journal of pharmacology and experimental therapeutics · 2020Article
- A Novel LC-MS/MS Assay for Quantification of Des-carboxy Prothrombin and Characterization of Warfarin-Induced Changes.Clinical and translational science · 2020Article
- An Alaska Native community's views on genetic research, testing, and return of results: Results from a public deliberation.PloS one · 2020Article
- Power Sharing, Capacity Building, and Evolving Roles in ELSI: The Center for the Ethics of Indigenous Genomic Research.Collaborations (Coral Gables, Fla.) · 2020Article
- VKORC1 and Novel CYP2C9 Variation Predict Warfarin Response in Alaska Native and American Indian People.Clinical and translational science · 2019Article
- Changing the Conversation about The Ethics of Genomics and Health Disparities Research with American Indian and Alaska Native Communities: A Report from the Field.Journal of health care for the poor and underserved · 2019Article
- Responsible Research With Urban American Indians and Alaska Natives.American journal of public health · 2018Review
- Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People.Clinical and translational science · 2018Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
objectivesPharmacogenetic testing is projected to improve health outcomes and reduce the cost of care by increasing therapeutic efficacy and minimizing drug toxicity. American Indian and Alaska Native (AI/AN) people historically have been excluded from pharmacogenetic research and its potential benefits, a deficiency we sought to address. The vitamin K antagonist warfarin is prescribed for prevention of thromboembolic events, although its narrow therapeutic index and wide interindividual variability necessitate close monitoring of drug response. Therefore, we were interested in variation in CYP2C9, VKORC1, CYP4F2, CYP4F11, and GGCX, which encode enzymes important for the activity of warfarin and synthesis of vitamin K-dependent blood clotting factors.
methodsWe resequenced these genes in 188 AI/AN people in partnership with Southcentral Foundation in Anchorage, Alaska and 94 Yup'ik people living in the Yukon-Kuskokwim Delta of southwest Alaska to identify known or novel function-disrupting variation. We conducted genotyping for specific single nucleotide polymorphisms in larger cohorts of each study population (380 and 350, respectively).
resultsWe identified high frequencies of the lower-warfarin dose VKORC1 haplotype (-1639G>A and 1173C>T) and the higher-warfarin dose CYP4F2*3 variant. We also identified two relatively common, novel, and potentially function-disrupting variants in CYP2C9 (M1L and N218I), which, along with CYP2C9*3, CYP2C9*2, and CYP2C9*29, predict that a significant proportion of AI/AN people will have decreased CYP2C9 activity.
conclusionOverall, we predict a lower average warfarin dose requirement in AI/AN populations in Alaska than that seen in non-AI/AN populations of the USA, a finding consistent with clinical experience in Alaska.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.