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Polymorphic variations in the expression of the chemical detoxifying UDP glucuronosyltransferases

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dc.contributor.authorMackenzie, P.
dc.contributor.authorGregory, P.
dc.contributor.authorLewinsky, R.
dc.contributor.authorYasmin, S.
dc.contributor.authorCrittenden, T.A.
dc.contributor.authorMcKinnon, R.A.
dc.contributor.authorGardner Stephen, D.
dc.date.issued2005
dc.description.abstractThe UDP glucuronosyltransferases (UGT) are expressed predominantly in the liver and gastrointestinal tract in humans. Their expression varies widely between individuals, due in part to coding region polymorphisms that alter catalytic function and in part, to differences in the regulation of UGT genes. The latter differences are most likely the result of polymorphisms in the regulatory elements of UGT genes and in the transcription factors that bind to these elements. Several frequent polymorphisms in the promoters of UGT genes have been described; however, few of these fall within critical regulatory elements and alter UGT expression. Some rare mutations alter UGT promoter activity in in vitro systems but their effect in the clinic is still to be confirmed. Several transcription factors that regulate UGT gene expression in cells of hepatic and intestinal origin have been identified. These include positive regulators of UGT gene expression such as hepatocyte nuclear factor 1 alpha (HNF1 alpha), octamer transcription factor-1 (Oct-1) and the intestine-specific transcription factor, caudal-related homeodomain protein 2 (Cdx2). Negative regulators include the Pre B cell homeobox factor (Pbx2) and its dimerization partner, Pbx regulating protein 1 (Prep1). Polymorphisms in these transcription factors may cause differences in their interaction and binding to UGT promoters. Current work describing the effects of these transcription factor polymorphisms on UGT expression will be described. Knowledge of UGT promoter elements and the proteins that bind to these elements, as well as knowledge of polymorphisms that alter their function, may aid in the prediction of an individual's response to chemicals and in the prediction of chemical toxicities.
dc.identifier.citationToxicology and Applied Pharmacology, 2005; 207(2 SUPPL.):77-83
dc.identifier.doi10.1016/j.taap.2004.12.026
dc.identifier.issn0041-008X
dc.identifier.issn1096-0333
dc.identifier.orcidGregory, P. [0000-0002-0999-0632]
dc.identifier.urihttps://hdl.handle.net/1959.8/27283
dc.language.isoen
dc.publisherElsevier
dc.rightsCopyright status unknown
dc.source.urihttps://doi.org/10.1016/j.taap.2004.12.026
dc.subjectUDP glucuronosyltranferases
dc.subjectgene regulation
dc.subjectpharmacogenetics
dc.subjectpharmacogenomics
dc.subjectHumans
dc.subjectGlucuronosyltransferase
dc.subjectTranscription Factors
dc.subjectGene Expression Regulation, Enzymologic
dc.subjectMetabolic Detoxication, Drug
dc.subjectPolymorphism, Genetic
dc.subjectPromoter Regions, Genetic
dc.titlePolymorphic variations in the expression of the chemical detoxifying UDP glucuronosyltransferases
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9915912110301831

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