Allan Rettie

About

Allan Rettie is a Professor in the Department of Medicinal Chemistry at the University of Washington School of Pharmacy. He obtained his PhD in Pharmaceutical Sciences from the University of Newcastle-upon-Tyne, England, in 1983, and completed postdoctoral research at the University of Washington focusing on extra-hepatic drug metabolism and mechanisms of drug-drug interactions. He joined the UW faculty in 1987 and served as Department Chair from 2000 to 2014. His research primarily centers on the biochemistry and pharmacogenetics of human cytochrome P450 enzymes, with particular emphasis on understanding mechanisms of catalysis, substrate specificity, pharmacogenetic variability, and adverse drug reactions related to these enzymes. Rettie’s work has significantly contributed to elucidating how genetic polymorphisms influence drug metabolism, especially concerning the anticoagulant warfarin, and has explored the roles of CYP4 family enzymes in health and disease. He has published extensively, served on numerous editorial boards, and received awards such as the North American Scientific Achievement Award from ISSX and fellowship in the Japanese Society for the Study of Xenobiotics.

Research topics

• Genetics
• Biology
• Psychiatry
• Medicine
• Dermatology
• Pharmacology
• Internal medicine
• Pathology

Selected publications

• Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for <i>CYP2C9</i> and <i>HLA‐B</i> Genotypes and Phenytoin Dosing: 2020 Update

  Clinical Pharmacology & Therapeutics · 2020 · 170 citations

  Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for the use of phenytoin based on CYP2C9…

  DOI

• Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact

  eLife · 2020 · 101 citations

  Vitamin K epoxide reductase (VKOR) drives the vitamin K cycle, activating vitamin K-dependent blood clotting factors. VKOR is also the target of the widely used anticoagulant drug, warfarin. Despite VKOR's pivotal role in coagulation, its structure and active site remain poorly understood. In addition, VKOR variants can cause vitamin K-dependent clotting factor deficiency or alter warfarin response. Here, we used multiplexed, sequencing-based assays to measure the effects of 2,695 VKOR missense…

  DOI

• Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff

  Genetics · 2024-09-25 · 12 citations

  articleOpen access

  The cytochrome P450s enzyme family metabolizes ∼80% of small molecule drugs. Variants in cytochrome P450s can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across cytochrome P450s is challenging. Even closely related cytochrome P450s like CYP2C9 and CYP2C19, which share 92% amino acid sequence identity, display distinct phenotypic properties. Using variant abundance by massively para…

  PublisherOA PDFDOI

• There and Back Again: A Perspective on 20 Years of CYP4Z1

  Drug Metabolism and Disposition · 2024-04-11 · 6 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Experimental pharmacology in precision medicine

  Pharmacology Research & Perspectives · 2023-10-26 · 6 citations

  articleOpen access

  Following the initial sequencing of the human genome, it was widely predicted that this knowledge would lead to transformational advances in the identification, prevention, and treatment of disease.1 The terms “Precision Medicine” and “Personalized Medicine” have been used interchangeably over the last two decades to describe almost all applications of genomic information in the development and use of medicinal interventions.2 While there are notable clinical advances that exemplify the highly e…

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM068797

  NIH · $2.3M · 2012

• NIH Grant R01GM049054

  NIH · $3.7M · 2011

• Drug Action, Metabolism and Kinetics Training Grant

  NIH · $14.8M · 1979–2024

Frequent coauthors

• Kenneth E. Thummel

  University of Washington

  88 shared

• William Trager

  56 shared

• Helmut Hanenberg

  University of Duisburg-Essen

  47 shared

• Matthew G. McDonald

  University of Washington

  44 shared

• Catherine K. Yeung

  University of Washington

  43 shared

• Mary F. Paine

  Washington State University Spokane

  40 shared

• Constanze Wiek

  Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde

  39 shared

• Andrea Gaedigk

  University of Missouri–Kansas City

  38 shared

Labs

• Student Success TeamPI

Education

• Ph.D., Pharmaceutical Sciences

  University of Newcastle-upon-Tyne

• B.S.

  Heriot-Watt University

Awards & honors

• North American Scientific Achievement Award from ISSX (2005)
• Fellow of the Japanese Society for the Study of Xenobiotics…

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