ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy
- 1 June 2005
- Vol. 54 (6), 829-834
- https://doi.org/10.1136/gut.2004.058115
Abstract
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 (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). To establish whether mutations in ATP8B1 are associated with ICP in British cases Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P 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. 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.Keywords
This publication has 47 references indexed in Scilit:
- Characterization of mutations in ATP8B1 associated with hereditary cholestasisHepatology, 2004
- Obstetric cholestasis, outcome with active management: a series of 70 casesBJOG: An International Journal of Obstetrics and Gynaecology, 2002
- Familial intrahepatic cholestasis 1: Studies of localization and functionHepatology, 2001
- A Missense Mutation In Fic1 Is Associated With Greenland Familial CholestasisHepatology, 2000
- In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and electron microscopy in chronic ductopenic rejection of human liver allograftsGut, 1998
- Development and applications of in vivo clinical magnetic resonance spectroscopyProgress in Biophysics and Molecular Biology, 1996
- Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models.Gut, 1996
- ABC Transporters: From Microorganisms to ManAnnual Review of Cell Biology, 1992
- A general approach to selection of multiple cubic volume elements using the ISIS techniqueMagnetic Resonance in Medicine, 1988
- Ethinylestradiol administration selectively alters liver sinusoidal membrane lipid fluidity and protein compositionBiochemistry, 1988