Document Detail


Sequencing and functional assessment of hPXR (NR1I2) variants in intrahepatic cholestasis of pregnancy.
MedLine Citation:
PMID:  18800312     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. The purpose of this study was to evaluate the role of coding variation in hPXR (NR1I2) in intrahepatic cholestasis of pregnancy (ICP) and to functionally asses the response of PXR variants to ligands of interest in ICP. 2. The coding region of hPXR was sequenced in a cohort of 121 Caucasian ICP patients and exon 2 was sequenced in an additional 226 cases. Reporter assays were used to evaluate the function of all known hPXR variants in response to the secondary bile acid lithocholic acid and therapeutic agents rifampicin, ursodeoxycholic acid and dexamethasone. 3. Two coding single nucleotide polymorphisms (C79T and G106A) were detected in the ICP cohort at frequencies consistent with healthy populations. These do not alter hPXR function in response to ligands of interest to ICP. Analysis of all known coding hPXR variants demonstrates that while subtle changes in experimental design mask or may unveil the functional effects of genetic variation, these are not maintained in a standard functional assay. 4. Coding genetic variation in hPXR does not contribute to the aetiology of ICP in Caucasian populations.
Authors:
B M Owen; S W C Van Mil; M Boudjelal; I McLay; W Cairns; E Elias; R White; C Williamson; P H Dixon
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  38     ISSN:  1366-5928     ISO Abbreviation:  Xenobiotica     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-14     Completed Date:  2008-12-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  England    
Other Details:
Languages:  eng     Pagination:  1289-97     Citation Subset:  IM    
Affiliation:
Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Female
Genetic Predisposition to Disease / genetics*
Genetic Variation / genetics*
Humans
Molecular Sequence Data
Pregnancy
Pregnancy Complications / genetics*
Receptors, Steroid / genetics*
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council
Chemical
Reg. No./Substance:
0/Receptors, Steroid; 0/pregnane X receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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