Neonatal hyperbilirubinemia and a common mutation of the bilirubin uridinediphosphate-glucuronosyltransferase gene in Japanese

Neonatal hyperbilirubinemia, which is prevalent among Asian peoples, has be en considered as a physiological phenomenon, and its metabolic basis has no t been clearly explained. Gilbert syndrome is a common inherited disease of unconjugated hyperbilirubinemia due to decreased bilirubin uridine diphosp hate-glucuronosyltransferase (B-UGT), and its role in neonatal jaundice has recently been considered. We have previously reported that the Gly71Arg mu tation of the B-UGT gene associated with Gilbert syndrome is prevalent in J apanese, Korean, and Chinese populations and was more frequently detected i n neonates with severe hyperbilirubinemia than in control subjects. We have studied 159 Japanese full-term neonates, evaluating the relationship betwe en the B-UGT genotype and the severity of jaundice, as assessed with a tran scutaneous bilirubinometer. The gent: frequency of the Gly71Arg mutation in these neonates was 0.19. and neonates carrying the Gly71Arg mutation had s ignificantly increased bilirubin levels on days 2-4, manifested in a gene d ose-dependent manner. The frequency of the Gly71Arg mutation was 0.47 in th e neonates who required phototherapy (i.e., those with more severe hyperbil irubinemia), significantly higher than 0.16 in the neonates who did not req uire the therapy. The gene frequency of the TA repeat promoter polymorphism the (TA)(7) mutation, was 0.07, and neonates carrying this mutation did no t have an increase in bilirubin. These results suggested that the Gly71Arg mutation contributes to the high incidence of neonatal hyperbilirubinemia i n Japanese.