Clinical Pharmacology and Pharmacogenetics in a Genomics Era: The DMET Platform

Abstract

While no genome-wide pharmacogenetics study has yet been published, the field of pharmacogenetics is moving towards exploratory, large-scale analyses of the interaction between genetic variation and drug treatment. The Drug Metabolizing Enzymes and Transporters (DMET) platform offers a standardized set of 1936 variants in 225 genes related to drug absorption, distribution, metabolism and elimination that is useful to scan the genome for previously unknown associations between variation in absorption, distribution, metabolism and elimination genes and pharmacokinetic and pharmacodynamic outcomes of drug treatment. The purpose of this review is to put the DMET platform into context within the current study designs that have been used in pharmacogenetics, and to explore the role that DMET has played – and will play – in future pharmacogenetics studies.

KEYWORDS::

• DMET
• genome-wide association study
• pharmacogenetics
• pharmacokinetics
• toxicity

Financial & competing interests disclosure

Tristan Sissung, William Figg and John Deeken served as consultants for Affymetrix and reviewed the accuracy and relevance of genes and genetic variants included on the DMET Plus panel prior to its public release in 2008. Tristan Sissung and William Figg complied with NIH policy regarding compensation to federal employees. No further ongoing financial relationships exist between the authors and Affymetrix. This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Bethesda, MD, USA. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the US Government. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

DMET: Drug Metabolizing Enzymes and Transporters. Modified from [11].

Additional information

Funding

Tristan Sissung, William Figg and John Deeken served as consultants for Affymetrix and reviewed the accuracy and relevance of genes and genetic variants included on the DMET Plus panel prior to its public release in 2008. Tristan Sissung and William Figg complied with NIH policy regarding compensation to federal employees. No further ongoing financial relationships exist between the authors and Affymetrix. This study was supported in part by the Intramural Research Program of the National Institute of Health (NIH), National Cancer Institute, Bethesda, MD, USA. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the US Government. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.