TATA-box mutant in the promoter of the uridine diphosphate glucuronosyltransferase gene in Italian patients with Gilbert's syndrome.

Background: A mutation in the promoter of the uridine diphosphate glucuronosyltransferase gene has been described in patients with Gilbert's syndrome from Northern Europe.

Aims: To assess the frequency of this mutation in Italian patients with Gilbert's syndrome and in normal controls, in order to establish the molecular basis and molecular epidemiology of the syndrome in Italy.

Patients: Forty-six patients with a clinical diagnosis of Gilbert's syndrome and 44 individuals from the general population unselected for bilirubin levels.

Methods: Polymerase chain reaction amplification of the TATA-box element in the promoter of uridine diphosphate glucuronosyltransferase and identification of wild-type and variant alleles by high-resolution polyacrylamide gel electrophoresis.

Results: A TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase was found on 93% of chromosomes from patients with Gilbert's syndrome. The same variant was present on 44% of chromosomes from controls, unselected for bilirubin levels. Only 55% of controls homozygous for the TATA-box variant, however, had increased bilirubin levels.

Conclusions: The TATA-box variant in the promoter of uridine diphosphate glucuronosyltransferase is strongly associated with the phenotype of Gilbert's syndrome in Italy. The incomplete penetrance of the mutation observed in controls indicates that other acquired or inherited conditions affecting bilirubin production, uptake, cellular transport or excretion may contribute to the hyperbilirubinaemia of Gilbert's syndrome.