HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Müllenbach, R Articles by Williamson, C Search for Related Content PubMed PubMed Citation Articles by Müllenbach, R Articles by Williamson, C

ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy

¹ Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, UK
² Imperial College Genetics and Genomics Research Institute, Imperial College London, Hammersmith Hospital, London, UK
³ Robert Steiner MRI Unit, MRC Clinical Sciences Centre, and Division of Medicine A, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK
⁴ King George Hospital, Ilford, Essex, UK

Correspondence to:
Correspondence to:
Dr C Williamson
Maternal and Fetal Disease Group, 3rd Floor IRDB, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK; catherine.williamson{at}imperial.ac.uk

ABSTRACT
Background: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC).

Aims: To establish whether mutations in ATP8B1 are associated with ICP in British cases

Patients: Sixteen well phenotyped women with ICP without raised -GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected.

Methods: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic ³¹P magnetic resonance spectroscopy (MRS)

Results: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls.

Conclusions: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.

Abbreviations: ICP, intrahepatic cholestasis of pregnancy; PFIC, progressive familial intrahepatic cholestasis; BRIC, benign recurrent intrahepatic cholestasis; MRS, magnetic resonance spectroscopy; -GT, gamma-glutamyl transpeptidase; NTP, nucleotide or nucleoside triphosphate; PME, phosphomonoester; PDE, phosphodiester; GPC, glycerophosphorylcholine; GPE, glycerophosphorylethanolamine; ABC, ATP binding cassette; PCR, polymerase chain reaction; IQR, interquartile range

Keywords: bile; liver; magnetic resonance spectroscopy; intrahepatic cholestasis of pregnancy

This article has been cited by other articles:

				H E Wasmuth, A Glantz, H Keppeler, E Simon, C Bartz, W Rath, L-A Mattsson, H-U Marschall, and F Lammert Intrahepatic cholestasis of pregnancy: the severe form is associated with common variants of the hepatobiliary phospholipid transporter ABCB4 gene Gut, February 1, 2007; 56(2): 265 - 270. [Abstract] [Full Text] [PDF]