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J Pharm Sci. 2013 Sep;102(9):2924-9. doi: 10.1002/jps.23483. Epub 2013 Feb 21.

Gene-gene-environment interactions between drugs, transporters, receptors, and metabolizing enzymes: Statins, SLCO1B1, and CYP3A4 as an example.

Author information

1
Program in Pharmacogenomics, Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA. wolfgang.sadee@osumc.edu

Abstract

Pharmacogenetic biomarker tests include mostly specific single gene-drug pairs, capable of accounting for a portion of interindividual variability in drug response and toxicity. However, multiple genes are likely to contribute, either acting independently or epistatically, with the CYP2C9-VKORC1-warfarin test panel, an example of a clinically used gene-gene-dug interaction. I discuss here further instances of gene-gene-drug interactions, including a proposed dynamic effect on statin therapy by genetic variants in both a transporter (SLCO1B1) and a metabolizing enzyme (CYP3A4) in liver cells, the main target site where statins block cholesterol synthesis. These examples set a conceptual framework for developing diagnostic panels involving multiple gene-drug combinations.

KEYWORDS:

drug-metabolizing enzymes; genetic polymorphisms; membrane transport; pharmacogenomics; receptors

PMID:
23436703
DOI:
10.1002/jps.23483
[Indexed for MEDLINE]

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