Donor liver uridine diphosphate (UDP)-glucuronosyltransferase-1A1 deficiency causing Gilbert's syndrome in liver transplant recipients.
BACKGROUND
Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, has been attributed to two extra (TA) bases in the TATAA-box of the promoter region of its gene, where the A(TA)6TAA allele corresponds to the normal gene and A(TA)7TAA corresponds to a gene with reduced expression. Our aim was to determine whether isolated hyperbilirubinemia in liver transplant recipients was due to Gilbert's syndrome acquired through the liver allograft.


METHODS
From 305 patients followed in our Liver Transplant Clinic, five patients with isolated unconjugated hyperbilirubinemia in the absence of hemolysis, recurrent viral hepatitis, and biliary tract pathology were identified; 10 other post-orthotopic liver transplantion patients with normal liver chemistry tests were randomly selected as a control group. DNA was extracted from paraffin-embedded liver allograft tissue and peripheral lymphocytes and was genotyped for the TA repeat at the uridine diphosphate glucononosyltransferase-lA1 promoter region by polymerase chain reaction and acrylamide gel electrophoresis. Homozygosity for the (TA)7 allele was considered diagnostic of Gilbert's syndrome.


RESULTS
The mean serum total bilirubin level of the study patients was 2.28 mg/dl (range 1.8-3.0), consisting predominantly of the unconjugated form; that of the control patients was 0.76 mg/dl (range 0.4-1.1). The liver tissue from all five patients in the study group possessed the homozygous A(TA)7TAA genotype that was not observed in their lymphocytes. None of the liver tissue from the control patients demonstrated homozygosity for the A(TA)7TAA allele.


CONCLUSIONS
Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, causing Gilbert's syndrome, may be carried by the donor liver and present with isolated unconjugated hyperbilirubinemia in liver transplant recipients.
Te
H S
HS
Department of Medicine, University of Chicago Hospitals, Illinois 60637, USA.
Schiano
T D
TD
Das
S
S
Kuan
S F
SF
DasGupta
K
K
Conjeevaram
H S
HS
Baker
A L
AL
D000328:Adult; D000483:Alleles; D005260:Female; D005878:Gilbert Disease / Q000209:etiology*; D014453:Glucuronosyltransferase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D007527:Isoenzymes / Q000172:deficiency*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014019:Tissue Donors
D007527:Isoenzymes; D014453:Glucuronosyltransferase