title: Persistent unconjugated hyperbilirubinemia after liver transplantation due to an abnormal bilirubin UDP-glucuronosyltransferase gene promoter sequence in the donor.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Hepatology and Gastroenterology, University Hospital, Groningen, The Netherlands. p.l.m.jansen@med.rug.nl
authors.forename: P L
authors.initials: PL
authors.lastname: Jansen
authors.forename: P J
authors.initials: PJ
authors.lastname: Bosma
authors.forename: C
authors.initials: C
authors.lastname: Bakker
authors.forename: S P
authors.initials: SP
authors.lastname: Lems
authors.forename: M J
authors.initials: MJ
authors.lastname: Slooff
authors.forename: E B
authors.initials: EB
authors.lastname: Haagsma
mesh_terms: D000328:Adult; D005260:Female; D005878:Gilbert Disease / Q000201:enzymology / Q000209:etiology*; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016385:TATA Box; D014019:Tissue Donors
chemical_list: C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase