NWA PGRN Research

Scarlett Hopkins and Eliza Orr collecting data in the Yukon-Kuskokwim Delta, Alaska

Scarlett Hopkins and Eliza Orr collecting data in the Yukon-Kuskokwim Delta, Alaska

The Northwest-Alaska PGRN focuses on genetic variation among American Indian and Alaska Natives (AI/AN) and rural Pacific Northwest populations. We have created a 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 on the Flathead Reservation in 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 opportunities for the introduction of pharmacogenetics into patient care.


2017 Publications
Carnitine palmitoyltransferase 1A P479L and infant death: Implications of emerging data, by Fohner A, Garrison N, Austin M, Burke W.  Genetics in Medicine, 2017.

Association between iq’mik smokeless tobacco use and cardiometabolic risk among Yup’ik Alaska Native People, by Ryman TK, Boyer BB, Hopkins S, Philip J, Thompson B, Beresford SAA, Thummel KE and Austin MA.  Ethnicity and Health, 2017.

Impact of Body Mass Index and Genetics on Warfarin Major Bleeding Outcomes in a Community Setting, by Hart R, Veenstra DL, Boudreau DM and Roth JA.  American Journal of Medicine, 2017.

2015-2016 Publications
Partnership with the Confederated Salish and Kootenai Tribes: Establishing an Advisory Committee for Pharmacogenetic Research, by Morales CT, Muzquiz LI, Howlett K, Azure B, Bodnar B, Finley V, Incashola T, Mathias C, Laukes C, Beatty P, Burke W, Pershouse MA, Putnam EA, Trinidad SB, James R, Woodahl EL. Progress in Community Health Partnerships: Research, Education and Action,  2016.

Variation in genes controlling warfarin disposition and response in American Indian and Alaska Native People: CYP2C9, VKORC1, CYP4F2, CYP4F11, GGCX, by Fohner AE, Robinson R, Yracheta J, Dillard DA, Schilling B, Kahn B, Hopkins S, Boyer B, Black J, Wiener H, Tiwari H, Gordon A, Nickerson D, Tsai J, Farin FM, Thornton TA, Rettie AE, and Thummel KE.  Pharmacogenetics and Genomics, 2015. 

Variability in expression of human CYP3A5 in human fetal liver, by Vyhlidal CA, Pearce RE, Gaedigk R, Shuster DL, Calamia JC, Thummel KE and Leeder JS.  Drug Metab Disp, 2015

The CYP2C19 intron2 branch point SNP is the oldest polymorphism contributing to the poor metabolizer phenotype in livers with CYP2C19*35 and CYP2C19*2 alleles, by Chaudry AS, Prasad B, Shirasaka Y, Fohner A, Finkelstein D, Fan Y, Wang S, Wu G, Aklillu E, Sim S, Ingelman-Sundberg M, Thummel KE and Schuetz EG.  Drug Metab Disp, 2015.

Inter-individual variability of hepatic microsomal CYP2C19 activity due to differences in gene diplotypes and P450 oxidoreductase content, by Shirasaka Y, Chaudhry AS, McDonald M, Prasad B, Wong T, Calamia JC, Fohner A, Thornton TA, Isoherranen N, Unadkat J, Rettie AE, Schuetz EG and Thummel KE. The Pharmacogenomics Journal, 2016.

Associations between Diet and Cardio-metabolic Risk among Yup’ik Alaska Native People using Food Frequency Questionnaire Dietary Patterns, by Ryman TK, Boyer BB, Hopkins S, Phillip J, Beresford SAA, Thompson B, Heagerty PJ, Thummel K, Austin MA.  Nutrition, Metabolism & Cardiovascular Diseases, 2015.

Genetics, diet, and season are associated with serum 25-hydroxylated cholecalciferol concentration in a Yup’ik study population from southwestern Alaska, by Fohner AE, Wang Z, Yracheta J, O’Brien D, Hopkins SE, Boyer BB, Black J, Wiener HW, Tsai J, Janssen P, Austin M, Thornton T, Thummel KE. J Nutrition, 2016.

Prenatal pharmacogenetics: a promising area of research, by Dorfman E., Thummel KE, Hebert MF, Thummel KE, Wang E and Burke W, Hebert MF.  The Pharmacogenomics Journal, 2016.

Extracting electronic health record data in a practice-based research network: Processes to support translational research across diverse practice organizations, by Cole AM, Stephens KA, Keppel GA, Esteri H and Baldwin LM.  EGEMS (Wash DC). 2016.

Decline in traditional marine food intake and vitamin D levels from the 1960’s to present in young Alaska Native (Yup’ik) women, by O’Brien, DM, Thummel KE, Bulkow L, Wang Z, Corbin B, Klejka J, Boyer B, Hennessey T and Singleton, R.  Public Health Nutrition, 2016.

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci and interactions with dietary n-3 polyunsaturated fatty acids, by Aslibekyan S, Vaughan LK, Wiener HW, Lemas, DJ, O’Brien DM, Hopkins S, Thummel KE, Kimber L. Stanhope KL, Havel PJ, Allison DB, Boyer BB and Tiwari HK.  Genes & Nutrition, 2016.

Implementing Precision Medicine: The Ethical Challenges by Korngiebel DM, Thummel KE and Burke W. Trends in Pharmacological Sciences, 2016.

Predictors of variation in CYP2A6 mRNA, protein and enzyme activity in a human liver bank: influence of genetic and non-genetic factors, byTanner J-A, Prasad B, Claw, K, Stapleton P, Chaudry AS, Schuetz EG, Thummel KE and Tyndale RF. J Pharmacology and Experimental Therapeutics, 2016.

2014 Publications:
A Call for Accurate Pharmacogenetic Labeling: Telling It Like It Is, by Burke W, Thummel KE. JAMA Internal Medicine, 2014.

Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing, by Caudle KE, Rettie AE, et al. Clinical Pharmacology and Therapeutics, 2014.

Human UGT1A4 and UGT1A3 conjugate 25-hydroxyvitamin D3: metabolite structure, kinetics, inducibility and interindividual variability, by Wang ZH, Thummel KE, et al. Endocrinology, 2014.

Pharmacogenetic research in partnership with American Indian and Alaska Native Communities, by Woodahl EL, Lesko L, Hopkins S, Robinson RF, Thummel KE, Burke W. Pharmacogenomics, 2014.

A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites, by Haque JA, Rettie AE, et al. Blood, 2014.

Genetic risk factors for major bleeding in patients treated with warfarin in a community setting, by Roth JA, Boudreau D, Fujii MM, Farin FM, Rettie AE, Thummel KE, Veenstra DL. Clinical Pharmacology and Therapeutics, 2014.

Exploring Pathways to Trust: A Tribal Perspective on Data Sharing, by James RD, Dillard DA, Muzquiz L, Whitener R, Olsen P, Burke W, et al. Genetics in Medicine, 2014.

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGEnet systematic review, by Canestro WJ, Austin MA, Thummel KE. Genetics in Medicine, 2014.

Improving the efficiency and relevance of evidence-based recommendations in the era of whole-genome sequencing: an EGAPP methods update, by Veenstra DL, et al. Genetics in Medicine, 2013.

Building partnerships in community-based participatory research: budgetary and other cost considerations, by Hopkins SE, Burke W, Trinidad SB, Hopkins SE, Boyer BB, et al. Health Promotion Practice, 2014.

2013 Publications
Pharmacogenetics in American Indian populations: analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai Tribes, by Fohner A, Muzquiz LI, Austin MA, et al, Pharmacogenetics and Genomics, 2013.

CYP4 enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid ω-hydroxylase activities, by Edson KZ, Rettie AE. Current Topics in Medicinal Chemistry, 2013.

Cytochrome P450-dependent catabolism of vitamin K: w-hydroxylation catalyzed by human CYP4F2 and CYP4F11, by Edson KZ, Rettie AE. Biochemistry, 2013.

Risk, reward, and the double-edge sword: perspectives on pharmacogenetic research and clinical testing among Alaska Native people, by Shaw JL, Robinson RR, Starks H, Burke W, Dillard DA. American Journal of Public Health, 2013.

Additional Publications
Pharmacogenetics in American Indian populations: analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai Tribes, by Fohner A, Muzquiz LI, Austin MA, et al, Pharmacogenetics and Genomics, 2013.

Measurement and Compartmental Modeling of the Effect of CYP3A5 Gene Variation on Systemic and Intrarenal Tacrolimus Disposition by Zheng S, Tasnif Y, Hebert MF, et al, CPT, 2012.

Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis by Danese E, Montagnana M, Johnson JA, Rettie AE, et al, CPT, 2012.

Practical Ethics: Establishing a pathway to benefit for complex pharmacogenomic tests by Haga, SB and Burke, W, CPT, 2011.

Evolving Rearch and Stakeholder Perspectives on Pharmacogenomics by Beitelshees, AL and Veenstra, DL, JAMA, 2011.

Ethical Issues in Developing Pharmacogenetic Research Partnerships With American Indigenous Communities. by Boyer, BB et al, CPT, 2011.

Genomic research and wide data sharing: Views of prospective participants. by Trinidad, SB et al, Genetics In Medicine, 2010.

Pharmacogenomic trial design: use of a PK/PD model to explore warfarin dosing interventions through clinical trial simulation. by Salinger, DH et al, Pharmacogenetics and Genomics, 2009.

CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant. by McDonald, MG et al, Molecular Pharmacology, 2009.

The Center for Alaska Native Health Research Study: a community-based participatory research study of obesity and chronic disease-related protective and risk factors. by Mohatt, GV et al, Int J Circumpolar Health, 2007.

Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. by Rieder, MJ et al, N Engl J Med, 2005.

Recent Talks by NWA-PGRN Investigators

Follow this link from March 14, 2011 to hear Ken Thummel, Wylie Burke, and Rose James speak about: Using Genomics to Individualize Drug Therapy: Technical, Clinical, and Ethical Challenges

Frequently Asked Questions about Pharmacogenomics

To find out more about the science behind pharmacogenomics, please follow this link to Background or the Pharmacogenomics Factsheet

CPIC Guidelines

Ken Thummel and Dave Eaton

Ken Thummel and Dave Eaton