UDP-glucuronosyltransferase in Gilbert's syndrome

The diagnosis of Gilbert's syndrome, a condition characterised by mild jaundice related to chronic unconjugated hyperbilirubinemia, is often presumptive and the pathogenesis is incompletely understood. It would be of interest to develop an immunohistochemical staining method to confirm a diagnosis of Gilbert's syndrome. To this end liver tissues from ten patients with a presumed diagnosis of Gilbert's syndrome and six normal controls were examined by immunohistochemistry with polyclonal antibodies raised to UDP-glucuronosyltransferase (UGT). All subjects had normal liver biopsies by hemotoxylin and eosin staining. In normal human liver specific staining for UGT was seen diffusely in all hepatocytes of the hepatic lobule with zone 3 accentuation. There was a reduction of immunostaining throughout the hepatic lobule in all specimens from patients with Gilbert's syndrome and faint residual staining was seen in zone 3. This thus proved a useful method to confirm a clinical diagnosis of Gilbert's syndrome. Raising monospecific antibodies to UGT may give an insight into polypmorphisms of phase II drug metabolism. Bosma at al. have recently provided evidence from in vitro studies that subjects with Gilbert's syndrome have a putative defect in the promoter region of the gene encoding UDP-glucuronosyltransferase 1, resulting in reduced transcription. These studies have yet to be confirmed from human biopsy specimens and the possibility of second mutations in intronic sequences affecting the stability of UDP-glucuronosyltransferase 1 m RNA are being explored.