Neonatal hyperbilirubinemia and the bilirubin uridine diphosphate-glucuronosyltransferase gene:: The common -3263T>G mutation of phenobarbital response enhancer module is not associated with the neonatal hyperbilirubinemia in Japanese

Background: Neonatal hyperbilirubinemia is frequent and severe in Japanese newborns. Previously, it has been reported that half of the Japanese neonates with severe hyperbilirubinemia carried the 211 G > A (p.G71R) mutation of the bilirubin uridine diphosphate-glueuronosyltransferase (UGT1A1) gene causing Gilbert syndrome. Recently, it was reported that the -3263T>G mutation in the phenobarbital response enhancer module in UGT1A1 was associated with the majority of cases of Gilbert syndrome. The gene frequency of the -3263T > G Mutation was determined and the relation with neonatal hyperbilirubinemia in Japanese was studied. Methods: UGT1A1 in 119 neonates born at Yamagata University Hospital, Yamagata, Japan, and 26 subjects who had undergone phototherapy due to severe hyperbilirubinemia at four other hospitals were studied. The gene frequency of -3263T > G mutation in Japanese, Korean, Chinese and German healthy adult controls was also determined. Hyperbilirubinemia was assessed with a Jaundice Meter and UGT1A1 was analyzed by sequence determination or restriction enzyme method. Results: The gene frequency of the -3263T > G mutation was 0.26 in Japanese subjects and was similar to the prevalence in Korean, Chinese and German populations. However, there was no significant increase in the gene frequency of the mutation in the neonates who required phototherapy for hyperbilirubinemia compared to that in the neonates without severe hyperbilirubinemia. In addition, neonates with or without the mutation did not show a significant change in the level of bilirubin and the mutation also did not show a synergic effect with the 211 G > A mutation on the level of bilirubin. Conclusion: The -3263T > G mutation is not likely to be associated with the neonatal hyperbilirubinemia in Japanese.