Severe hepatocellular dysfunction in obstetric cholestasis related to combined genetic variation in hepatobiliary transporters.
Obstetric cholestasis (OC) is a cholestatic disorder with a prominent genetic background including variation in diverse hepatobiliary lipid transporters, such as ABCB4 (phospholipids) and ABCB11 (bile salts). Given a marked hepatocellular dysfunction in an OC patient indicated by > 40-fold rise in alanine aminotransferase activity and minor gamma-glutamyl transpeptidase increases, we performed genotyping of candidate gene variants associated with adult cholestatic phenotypes. Genetic analysis revealed the heterozygous ABCB4 mutation p.R590Q, the ABCB11 variant p.V444A and the lithogenic ABCG8 variant p.D19H. Aggregation of multiple hepatobiliary transporter variants is rare in OC, and may cooperate to negatively modulate hepatobiliary transport capacities.
Department of Medicine II, Saarland University Hospital, Homburg, Germany. invzim@uks.eu
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Zimmer
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Krawczyk
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Mahler
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Weber
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Müllenbach
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Lammert
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D002779:Cholestasis / Q000201:enzymology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology / Q000235:genetics*
C093491:ABCB11 protein, human; C416946:ABCG8 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; C095122:multidrug resistance protein 3; D000410:Alanine Transaminase