Human Genetics

, Volume 115, Issue 6, pp 525–526 | Cite as

Two linked polymorphic mutations (A(TA)7TAA and T-3279G) of UGT1A1 as the principal cause of Gilbert syndrome

  • Yoshihiro Maruo
  • Carlos D′ Addario
  • Asami Mori
  • Masaru Iwai
  • Hiroko Takahashi
  • Hiroshi Sato
  • Yoshihiro Takeuchi
Short Report

Abstract

Gilbert syndrome is a mild hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). The mutation, A(TA)7TAA, is thought to be the sole cause of the syndrome in Caucasians, but an enhancer polymorphism (T-3279G) that lowers transcriptional activity has recently been reported. We have tested the linkage of the two mutations in 11 Caucasians and 12 Japanese patients who were homozygous for A(TA)7TAA. All 23 patients were also homozygous for T-3279G, indicating that T-3279G and A(TA)7TAA were linked. The decrease in transcription caused by both mutations together may be essential to the syndrome.

References

  1. Beutler E, Gelbart T, Demina A (1998) Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 95:8170–8174CrossRefPubMedGoogle Scholar
  2. Bosma PJ, Chowdhury JR, Bakker C, et al (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333:1171–1175CrossRefPubMedGoogle Scholar
  3. Maruo Y, Nishizawa K, Sato H, Doida Y, Shimada M (1999) Association of neonatal hyperbilirubinemia with bilirubin UDP-glucuronosyltransferase polymorphism. Pediatrics 103:1224–1227CrossRefPubMedGoogle Scholar
  4. Sugatani J, Yamakawa K, Yoshinari K, et al (2002) Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem Biophys Res Commun 292:492–497CrossRefPubMedGoogle Scholar
  5. Ueyama H, Koiwai O, Soeda Y, et al (1997) Analysis of the promoter of human bilirubin UDP-glucuronosyltransferase gene (UGT1*1) in relevance to Gilbert’s syndrome. Hepatol Res 9:152–163CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Yoshihiro Maruo
    • 1
  • Carlos D′ Addario
    • 3
  • Asami Mori
    • 1
  • Masaru Iwai
    • 1
  • Hiroko Takahashi
    • 1
  • Hiroshi Sato
    • 2
  • Yoshihiro Takeuchi
    • 1
  1. 1.Department of PediatricsShiga University of Medical Science OtsuJapan
  2. 2.Department of BioscienceShiga University of Medical ScienceOtsuJapan
  3. 3.Department of Pediatrics, San Carlos CentroEx-Medico Residente HospitalSanta FeArgentina

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