title: 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.
abstract: 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 211G > A (p.G71R) mutation of the bilirubin uridine diphosphate-glucuronosyltransferase (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 211G > A mutation on the level of bilirubin.
  
  
  CONCLUSIONS
  The -3263T > G mutation is not likely to be associated with the neonatal hyperbilirubinemia in Japanese.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Kanai
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kijima
authors.forename: Emi
authors.initials: E
authors.lastname: Shirahata
authors.forename: Ayako
authors.initials: A
authors.lastname: Sasaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Akaba
authors.forename: Kazuo
authors.initials: K
authors.lastname: Umetsu
authors.forename: Naohiro
authors.initials: N
authors.lastname: Tezuka
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kurachi
authors.forename: Shogo
authors.initials: S
authors.lastname: Aikawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D044466:Asian People / Q000235:genetics*; D005787:Gene Frequency; D005878:Gilbert Disease / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D007567:Jaundice, Neonatal / Q000208:ethnology / Q000235:genetics* / Q000628:therapy; D020125:Mutation, Missense; D016366:Open Reading Frames / Q000235:genetics; D010634:Phenobarbital / Q000494:pharmacology; D010789:Phototherapy; D011401:Promoter Regions, Genetic / Q000235:genetics; D020218:Response Elements / Q000235:genetics*; D016036:Seroepidemiologic Studies; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D010634:Phenobarbital; D000099148:UGT1A1 Enzyme