| Sequencing and functional assessment of hPXR (NR1I2) variants in intrahepatic cholestasis of pregnancy. | |
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MedLine Citation:
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PMID: 18800312 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Xenobiotica; the fate of foreign compounds in biological systems Volume: 38 ISSN: 1366-5928 ISO Abbreviation: Xenobiotica Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-14 Completed Date: 2008-12-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1306665 Medline TA: Xenobiotica Country: England |
Other Details:
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Languages: eng Pagination: 1289-97 Citation Subset: IM |
Affiliation:
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Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Steroid; 0/pregnane X receptor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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