RGD Reference Report - ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults. - Rat Genome Database

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ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults.

Authors: Ziol, Marianne  Barbu, Véronique  Rosmorduc, Olivier  Frassati-Biaggi, Annonciade  Barget, Nathalie  Hermelin, Brigitte  Scheffer, Georges L  Bennouna, Selma  Trinchet, Jean-Claude  Beaugrand, Michel  Ganne-Carrié, Nathalie 
Citation: Ziol M, etal., Gastroenterology. 2008 Jul;135(1):131-41. doi: 10.1053/j.gastro.2008.03.044. Epub 2008 Mar 26.
RGD ID: 14694975
Pubmed: PMID:18482588   (View Abstract at PubMed)
DOI: DOI:10.1053/j.gastro.2008.03.044   (Journal Full-text)


BACKGROUND & AIMS: Adenosine triphosphate-binding cassette subfamily B, member 4 (ABCB4) mutations have not been investigated in patients with unexplained cholestasis. We aimed to investigate ABCB4 mutations in adult patients with unexplained anicteric cholestasis and to describe liver injury associated with ABCB4 mutations.
METHODS: Between February 2004 and March 2007, all adults with unexplained cholestasis despite multiple investigations including liver biopsy and 124 healthy volunteers had ABCB4 sequencing. Fibrosis, bile duct lesions, inflammatory infiltrate, activation of myofibroblasts and multidrug-resistant P-glycoprotein 3 (MDR3) immunostaining were assessed on patients' liver biopsy specimens.
RESULTS: Thirty-two patients were included (23 females, 16-69 years of age). Eight different ABCB4 heterozygous mutations were found in 11 patients (34%). Seven of these mutations (exons 4, 6, 14, 18, 23) were never detected in the control group. One mutation (exon 15) was detected in 4 patients (12.5%) and 4 controls (3%). At the time of liver biopsy, the main clinical and biologic characteristics were similar in the 32 patients regardless of ABCB4 mutation. The histologic pattern in patients with a mutation consisted of portal fibrosis with ductular reaction and strong macrophagic infiltrate of portal tracts without significant periportal and lobular necroinflammatory lesions or cholangitis. Fibrosis score and macrophagic infiltration of portal tracts were significantly increased in patients with ABCB4 mutation (P = .01). Absence or reduced MDR3 canalicular immunostaining was demonstrated in all patients with ABCB4 mutations tested.
CONCLUSIONS: Heterozygous ABCB4 mutations were detected in 34% of adults with unexplained cholestasis, for the most part without biliary symptoms, and could result in significant liver fibrosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis severityIAGP 14694975associated with cholestasis and DNA:mutations: :RGD 
liver cirrhosis severityISOABCB4 (Homo sapiens)14694975; 14694975associated with cholestasis and DNA:mutations: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb4  (ATP binding cassette subfamily B member 4)

Genes (Mus musculus)
Abcb4  (ATP-binding cassette, sub-family B member 4)

Genes (Homo sapiens)
ABCB4  (ATP binding cassette subfamily B member 4)


Additional Information