Persistent unconjugated hyperbilirubinemia after liver transplantation due to an abnormal bilirubin UDP-glucuronosyltransferase gene promoter sequence in the donor

J Hepatol. 1997 Jul;27(1):1-5. doi: 10.1016/s0168-8278(97)80272-3.

Abstract

Background/aims: Gilbert's syndrome is genetically characterized by an extra TA element in the TATAA-box of the promotor region upstream of the bilirubin UDP-glucuronosyltransferase (UGT1A) coding region (Bosma et al. N Engl J Med 1995; 333: 1171-5). Persistent unconjugated hyperbilirubinemia is occasionally observed in liver transplant recipients with an otherwise normal liver function. We postulate that these patients could have received a liver from a donor with the Gilbert's syndrome genotype. Therefore, we investigated the UGT1A-gene TATAA-box in DNA from liver graft donors of jaundiced and non-jaundiced recipients.

Methods: DNA was obtained from stored donor lymphocytes and the number of TA elements in the TATAA-box of the UGT1A-gene promotor region was analyzed by polymerase chain-reaction.

Results: We observed two liver transplant recipients with persistent unconjugated hyperbilirubinemia. They received liver grafts from donors who were homozygous for an abnormal A(TA)7TAA-box in the UGT1A-gene. Four of 10 non-jaundiced recipients received livers from donors who were homozygous for the normal A(TA)6TAA-box and six received livers from donors who were heterozygous with a normal A(TA)6TAA-box on one allele and a prolonged A(TA)7TAA-box on the other allele.

Conclusions: This study shows that liver graft recipients with persistent unconjugated hyperbilirubinemia may have received a liver from a donor with an abnormal TATAA-box in the bilirubin UGT1A-gene promotor region.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Female
  • Gilbert Disease / enzymology
  • Gilbert Disease / etiology*
  • Glucuronosyltransferase / deficiency
  • Glucuronosyltransferase / genetics*
  • Humans
  • Liver / enzymology*
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic*
  • TATA Box
  • Tissue Donors

Substances

  • bilirubin glucuronoside glucuronosyltransferase
  • Glucuronosyltransferase