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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Liver-Enriched Transcription Factors and Their Role in Regulating UDP Glucuronosyltransferase Gene Expression

Author(s): D. A. Gardner-Stephen and P. I. Mackenzie

Volume 9, Issue 5, 2008

Page: [439 - 452] Pages: 14

DOI: 10.2174/138920008784746409

Price: $65

Abstract

Variations in the capacity to detoxify carcinogens and other environmental toxins, and to eliminate drugs and waste products of metabolism, are likely to have significant effects on health and drug efficacy. As the UDP glucuronosyltransferases metabolize many of these substances to less toxic glucuronides, variations in UGT expression are likely to be important in maintenance of health and therapeutic outcomes. The factors that regulate UGT gene expression are beginning to be identified. From among these factors, the Liver-Enriched Transcription Factors (LETFs), including Hepatocyte Nuclear Factors 1 and 4α, have a major role in UGT regulation in the major sites of drug metabolism, the liver and gastrointestinal tract. This review will describe what is currently known about these LETFs and their role in UGT gene expression. It is likely that polymorphisms in LETFs and the sites to which they bind in UGT genes, may impact on drug induced disease and drug therapy.

Keywords: UDP glucuronosyltransferase, liver-enriched transcription factors, hepatocyte nuclear factor, CAAT-enhancer binding protein, gene regulation


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