title: Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice.
abstract: OBJECTIVE
  To evaluate the role of bilirubin UDP-glucuronosyltransferase family 1, polypeptide A1 (UGT1A1) gene variations on prolonged unconjugated hyperbilirubinemia associated with breast milk feeding (breast milk jaundice [BMJ]).
  
  
  METHODS
  UGT1A1 gene allelic variation was analyzed in 170 Japanese infants with BMJ with polymerase chain reaction-direct sequencing, and their genotypes compared with serum bilirubin concentrations. In 62 of 170 infants, serum bilirubin concentration was followed after 4 months of life. Genotypes were examined in 55 infants without BMJ.
  
  
  RESULTS
  Of 170 infants with BMJ, 88 (51.8%) were homozygous UGT1A1*6. Serum bilirubin concentrations (21.8 ± 3.65 mg/dL) were significantly greater than in infants with other genotypes (P < .0001). The Gilbert UGT1A1*28 allele was not detected in infants with BMJ, except in an infant who was compound heterozygous with UGT1A1*6. At 4 months of age, serum bilirubin concentration improved to >1 mg/dL, except in 2 infants who were homozygous UGT1A1*7. Homozygous UGT1A1*6 was not detected in the control group.
  
  
  CONCLUSIONS
  One-half of the infants with BMJ were homozygous UGT1A1*6 and exhibited a serum bilirubin concentration significantly greater than other genotypes. This finding indicates that UGT1A1*6 is a major cause of BMJ in infants in East Asia. Previous finding have demonstrated that 5β-pregnane-3α,20β-diol present in breast milk inhibits p.G71R-UGT1A1 bilirubin glucuronidation activity. Thus, prolonged unconjugated hyperbilirubinemia may develop in infants with UGT1A1*6 who are fed breast milk.
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan. Electronic address: maruo@belle.shiga-med.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maruo
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Morioka
authors.affiliation: Department of Pediatrics, Hanwasumiyoshin General Hospital, Osaka, Japan; Department of Pediatrics, Hino Memorial Hospital, Kozukeda, Hino, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujito
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Nakahara
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Yanagi
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan; Department of Pediatrics, Hino Memorial Hospital, Kozukeda, Hino, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.affiliation: Department of Health and Nutrition, Faculty of Health and Human Life, Nagoya Bunri University, Inazawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Departments of Pharmacology, Chemistry, and Biochemistry, University of California San Diego, La Jolla, CA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Tukey
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeuchi
mesh_terms: D044466:Asian People / Q000235:genetics; D001663:Bilirubin / Q000097:blood*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics*; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000235:genetics*; D008297:Male; D008895:Milk, Human; D016133:Polymerase Chain Reaction; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme