Overview of Pharmacogenetics

David A. Katz1

1 Abbott Laboratories, Abbott Park, Illinois
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 6.10
DOI:  10.1002/0471141755.ph0610s36
Online Posting Date:  March, 2007
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Pharmacogenetics is the study of relationships between genetic variation and inter‐individual differences with respect to drug response. As the field has matured over the past 15 years, a remarkable diversity of pathways, variation types, and mechanisms have been found to be relevant pharmacogenetic factors. Today, pharmacogenetics is becoming more important in pharmacology for target validation, lead optimization, and understanding of idiosyncratic toxicity. This unit provides an overview of the history of pharmacogenetics and current research applications in drug discovery, as well as a discussion of research quality issues relevant to human subjects research in the pharmacogenetics laboratory.

Keywords: pharmacogenetics; genotype‐phenotype correlations; drug discovery; toxicogenomics; drug development

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Table of Contents

  • The Diversity of Pharmacogenetics
  • Applications in Drug Discovery
  • Applications in Drug Development
  • A Final Word: Technologies
  • Literature Cited
  • Figures
  • Tables
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Internet Resources
  Good clinical practice regulations promulgated by the International Committee for Harmonization.
  The Online Mendelian Inheritance in Man (OMIM) Web site. An annotated database containing information about genes and genetic variants. From the OMIM entry for a gene, it is possible to link to most other major Internet resources on that gene. This is the best place from which to gather gene‐centric information.
  PharmGKB, a database of candidate gene polymorphisms maintained via the NIH Pharmacogenetics Research Network (PRN). This group comprises investigators who are funded by a targeted NIGMS grant program. The site includes information about genes studied by PRN investigators, upcoming scientific meetings and the individual PRN centers. This information is also published on a regular basis in Pharmacological Reviews.
  The Clinical and Laboratory Standards Institute (CLIS, formerly NCCLS) homepage. This group is a globally recognized, voluntary consensus standards‐developing organization that enhances the value of medical testing within the healthcare community through the development and dissemination of standards, guidelines, and best practices. Guidance documents for laboratory quality may be purchased via their website.
  Homepage of the Human Cytochrome P450 Allele Nomenclature Committee. This is an up‐to‐date catalog of known sequence variants of human cytochromes P450. Unfortunately it does not include allele frequency, and lists rare alleles, even those that have been observed only once.
  Access to U.S. federal regulations related to drug development, diagnostic development, and diagnostic manufacturing.
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