Contribution of the TATA-Box Genotype (Gilbert Syndrome) to Serum Bilirubin Concentrations in the Italian Population

Abstract

Gilbert syndrome, a benign unconjugated hyperbilirubinemia without structural liver disease or overt hemolysis, is characterized by episodes of mild intermittent jaundice (1)(2)(3). Gilbert syndrome is the most common inherited variant of hepatic bilirubin metabolism, occurring in 2–12% of the population, and it is often detected in adulthood during routine blood tests. The most consistent feature in Gilbert syndrome is a deficiency in bilirubin glucuronidation, but the metabolism of drugs may also be affected(3). Recently, the molecular basis of Gilbert syndrome was elucidated and found to result from molecular lesions in one of the isoforms of the UDP-glucuronosyl transferase (UGT-1A) gene. UGT-1A is encoded by the UDG gene complex, which is composed of multiple unique forms of exon 1, each one specific for a single isoenzymes, and four common exons (from two to five) (4). UGT-1A is responsible for bilirubin glucuronidation; the other isoenzymes of the complex are involved in the metabolism of a number of aromatic compounds(5). The most common genetic alteration of UGT-1A is a TA insertion in the repetitive TATA-box of the …