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Semin Liver Dis 2001; 21(4): 551-562
DOI: 10.1055/s-2001-19033
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Role of Multidrug Resistance 3 Deficiency in Pediatric and Adult Liver Disease: One Gene for Three Diseases

Emmanuel Jacquemin
  • Hepatology Unit, Department of Pediatrics, and INSERM U 347, Centre Hospitalier Universitaire de Bicêtre, Paris, France
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Publication History

Publication Date:
17 December 2001 (online)

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ABSTRACT

Class III multidrug resistance P-glycoproteins, mdr2 in mice and MDR3 in humans, are canalicular phospholipid translocators involved in biliary phospholipid (phosphatidylcholine) excretion. The role of an MDR3 gene defect in liver disease was initially suspected in a subtype of progressive familial intrahepatic cholestasis called PFIC3. Several MDR3 mutations have been identified in children with PFIC3 and are associated with a low level of phospholipids in bile, leading to a high biliary cholesterol saturation index. Mutations leading to a truncated protein are associated with an absence of canalicular MDR3 protein. The phenotypic spectrum of PFIC3 ranges from neonatal cholestasis to cirrhosis in young adults. There is now strong evidence that in addition to PFIC3, an MDR3 defect can be involved in intrahepatic cholestasis of pregnancy and in cholesterol gallstone disease. Therefore, at least three human liver diseases are due to a single gene deficiency. Patients with PFIC3 due to MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates for cell therapy in the future.

KEYWORD

Multidrug resistance 3 - progressive familial intrahepatic cholestasis type 3 - gallstone - cholestasis of pregnancy - ursodeoxycholic acid

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