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Updated: Aug 18, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Polymorphisms of human nuclear receptors that control expression of drug-metabolizing enzymes
Allan B Okey1, Paul C Boutros, Patricia A Harper
1Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada. allen.okey@utoronto.ca
Abstract:
Phenotypic variation in human drug metabolism frequently can be attributed to polymorphisms in genes that encode drug-metabolizing enzymes (DMEs). However, levels of Phase I and Phase II DMEs also vary because many of these enzymes are induced by a myriad of xenobiotic chemicals. Individual differences in the capacity for induction contribute to variation in drug metabolism in human populations. Induction is mediated by intracellular receptors that act as ligand-dependent transcription factors, including several members of the nuclear receptor (NR) superfamily and the aryl hydrocarbon receptor (AHR). Genetic variations (SNPs and others) exist in genes that encode these human receptors but few of the known polymorphisms have any significant effect on enzyme induction. We suggest that the current scarcity of SNPs that are able to alter function in the DME-regulating NRs reflects considerable evolutionary selective pressures that conserve the key functional domains in these receptors.
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