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

[摘要] 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, me 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)(7)TAA-box in the UGT1A-gene, Four of 10 non-jaundiced recipients received livers from donors who were homozygous for the normal A(TA)(6)TAA-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)(7) TAA-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.

[发布日期] 1997-07-01

[关键词] Gilbert's syndrome;hyperbilirubinemia;jaundice;liver transplantation;TATAA box;UDP-glucuronosyltransferase