Gastroenterology (New York, N.Y. 1943), 1999-12, Vol.117 (6), p.1370-1379
1999
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- Autor(en) / Beteiligte
- Titel
- Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis
- Ist Teil von
- Gastroenterology (New York, N.Y. 1943), 1999-12, Vol.117 (6), p.1370-1379
- Ort / Verlag
- New York, NY: Elsevier Inc
- Erscheinungsjahr
- 1999
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Background & Aims: Progressive familial intrahepatic cholestasis (PFIC), an inherited liver disease of childhood, is characterized by cholestasis and either normal or increased serum γ-glutamyltransferase activity. Patients with normal γ-glutamyltransferase activity have mutations of the FIC1 locus on chromosome 18q21 or mutations of the BSEP gene on chromosome 2q24. Also, patients with bile acid synthesis defects have low γ-glutamyltransferase activity. We investigated expression of the bile salt export pump (BSEP) in liver samples from patients with a PFIC phenotype and correlated this with BSEP gene mutations. Methods: BSEP and multidrug resistance protein 2 (MRP2) expressions were studied by immunohistochemistry in liver specimens of 28 patients and BSEP gene mutation analysis in 19 patients. Bile salt kinetics were studied in 1 patient. Results: Sixteen of 28 liver samples showed no canalicular BSEP staining. Staining for MRP2 showed a normal canalicular pattern in all but 1 of these samples. Ten of 19 patients showed BSEP gene mutations; BSEP protein expression was lacking in all 10 patients. No mutations were found in 9 of 19 patients, and in all except 1, BSEP protein expression was normal. Bile salt concentration in bile of BSEP-negative/MRP2-positive PFIC patients was 0.2 ± 0.2 mmol/L (n = 9; <1% of normal) and in BSEP-positive PFIC patients 18.1 ± 9.9 mmol/L (n = 3; 40% of normal). The kinetic study confirmed the dramatic decrease of bile salt secretion in BSEP-negative patients. Conclusions: The findings show a close correlation between BSEP gene mutations and canalicular BSEP expression. Biliary secretion of bile salts is greatly reduced in BSEP-negative patients. GASTROENTEROLOGY 1999;117:1370-1379
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0016-5085eISSN: 1528-0012DOI: 10.1016/S0016-5085(99)70287-8Titel-ID: cdi_proquest_miscellaneous_69321176
- Format
- –
- Schlagworte
- ATP Binding Cassette Transporter, Subfamily B - genetics, ATP Binding Cassette Transporter, Subfamily B - metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics, ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 11, ATP-Binding Cassette Transporters - biosynthesis, ATP-Binding Cassette Transporters - genetics, ATP-Binding Cassette Transporters - metabolism, Bile Acids and Salts - metabolism, Biological and medical sciences, Cholestasis, Intrahepatic - enzymology, Cholestasis, Intrahepatic - genetics, Cholestasis, Intrahepatic - metabolism, Chromosomes, Human, Pair 18, DNA, Complementary - analysis, Female, gamma-Glutamyltransferase - metabolism, Gastroenterology. Liver. Pancreas. Abdomen, Genotype, Humans, Immunohistochemistry, Ion Pumps - biosynthesis, Ion Pumps - immunology, Kinetics, Liver. Biliary tract. Portal circulation. Exocrine pancreas, Male, Medical sciences, Mutation, Other diseases. Semiology, Phenotype, Polymerase Chain Reaction