Mutational analysis of the MRP2 gene and long-term follow-up of Dubin-Johnson syndrome in Japan.

Abstract

BACKGROUND:

Recent studies have indicated that dysfunction or loss of the multidrug resistance protein 2 (MRP2) is the molecular basis of Dubin-Johnson syndrome (DJS). To clarify the genetic basis of the disease and the long-term stability of serum bilirubin levels, we conducted a mutational analysis of the MRP2 gene and followed up serum bilirubin levels in Japanese DJS patients 30 years after they were originally diagnosed, based on traditional criteria.

METHODS:

Patients were interviewed by telephone, and blood tests, including a genetic analysis of MRP2, were performed on the patients and family members who gave informed consent.

RESULTS:

Over the 30 years, hyperbilirubinemia remained unchanged in four of the five patients studied, while it worsened in 1 patient whose DJS was complicated by chronic hepatitis C. From an MRP2 gene mutational analysis, six mutations, including the novel mutation 1177C>T, were found. Three patients of a consanguineous family were homozygotes for three mutations (298C>T, 1967+2T>C, and 2439+2T>C). Two patients were compound heterozygotes (1177C>T/2302C>T and 1967+2T>C/2026G>C). A familial study showed no difference in serum bilirubin levels between mutant/wild heterozygotes and wild/wild homozygotes.

CONCLUSIONS:

The hyperbilirubinemia of four Japanese patients with DJS, one of whom had a novel mutation, 1177C>T, of the MRP2 gene, had not worsened with aging.

• Authors: Ikuo Machida, Shinya Wakusawa, Fujiko Sanae, Hisao Hayashi, Atsushi Kusakabe, Hiroshi Ninomiya, Motoyoshi Yano, Kentaro Yoshioka
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 40 Issue 4 Pg. 366-70 (Apr 2005) ISSN: 0944-1174 [Print] Japan
• PMID: 15870973 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Genetic Markers
• P-glycoprotein 2
• DNA
• Bilirubin

Topics

• ATP Binding Cassette Transporter, Subfamily B (blood, genetics)
• Adult
• Alleles
• Bilirubin (blood)
• DNA (analysis, genetics)
• DNA Mutational Analysis
• Disease Progression
• Exons
• Female
• Follow-Up Studies
• Genetic Markers
• Genotype
• Humans
• Japan (epidemiology)
• Jaundice, Chronic Idiopathic (blood, epidemiology, genetics)
• Male
• Middle Aged
• Mutation
• Polymerase Chain Reaction
• Time Factors