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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Drug Metabolism and ...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Drug Metabolism and Disposition
Article . 2003 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Constitutive Androstane Receptor and Pregnane X Receptor Gene Expression in Human Liver: Interindividual Variability and Correlation with CYP2B6 mRNA Levels

Authors: Stelvio M. Bandiera; Jie Chen; Thomas K. H. Chang;

Constitutive Androstane Receptor and Pregnane X Receptor Gene Expression in Human Liver: Interindividual Variability and Correlation with CYP2B6 mRNA Levels

Abstract

The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) mediate the expression of mammalian cytochrome p450 (p450) 2B genes, including CYP2B6 in humans. Large interindividual differences exist in hepatic CYP2B6 expression, but the molecular basis for this variability is not well understood. In the present study, we developed real-time polymerase chain reaction methods to measure CYP2B6, CAR, and PXR mRNA expression and compared the levels in a panel of 12 individual human liver samples. The transcripts of CAR and CYP2B6 were present in all the samples analyzed, whereas those of PXR were detectable in all but one sample. A striking finding was the 240-fold interindividual variability in hepatic CAR mRNA levels, which was similar to the variability (278-fold) in CYP2B6 mRNA levels but greater than the 27-fold variability in PXR mRNA expression. Additional analysis revealed positive and statistically significant correlations between the mRNA levels of CAR and CYP2B6 (r(2) = 0.63, p = 0.002), PXR and CYP2B6 (r(2) = 0.75. p < 0.001), and CAR and PXR (r(2) = 0.86, p < 0.001). In summary, substantial interindividual differences exist in hepatic CAR and, to a lesser extent, PXR gene expression. The variability in the abundance of these transcription factors may contribute to the large interindividual differences in CYP2B6 gene expression in human liver.

Related Organizations
Keywords

Receptors, Steroid, Pregnane X Receptor, Genetic Variation, Receptors, Cytoplasmic and Nuclear, Oxidoreductases, N-Demethylating, Cytochrome P-450 CYP2B6, Gene Expression Regulation, Liver, Humans, Aryl Hydrocarbon Hydroxylases, RNA, Messenger, Constitutive Androstane Receptor, Transcription Factors

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
104
Top 10%
Top 10%
Top 1%