Gly71Arg mutation of the bilirubin UDP-glucuronosyltransferase 1A1 gene is associated with neonatal hyperbilirubinemia in the Japanese population.

The serum bilirubin level of Japanese newborn infants in their first few days is significantly higher than that in Caucasian newborn infants, suggesting that there might be genetic risk factors for the development of neonatal hyperbilirubinemia in the Japanese population. Recently, it has been reported that a variant TATA box in the promoter region of the bilirubin UDP-glucuronosyltransferase 1 (UGT1A1) gene is associated with the development of neonatal hyperbilirubinemia. This finding led us to the idea that a mutation, glycine to arginine at codon 71 (G71R), in the coding region of the UGT1A1 gene can cause neonatal hyperbilirubinemia. In this study, we determined the genotypic distribution of the G71R mutation in 72 Japanese newborn infants: 23 infants with hyperbilirubinemia and 49 infants without hyperbilirubinemia. In the hyperbilirubinemia group, 15 of 23 newborn infants had the G71R mutation (3 homozygotes and 12 heterozygotes), whereas in the non-hyperbilirubinemia group 16 of 49 newborn infants had the G71R mutation (1 homozygote and 15 heterozygotes). Therefore, the G71R mutation was present significantly more frequently in the hyperbilirubinemia group than in the non-hyperbilirubinemia group. This finding strongly suggests that the presence of the G71R mutation contributes to the development of neonatal hyperbilirubinemia in the Japanese population.