Bilirubin uridine diphosphate-glucuronosyltransferase variation is a genetic basis of breast milk jaundice

J Pediatr. 2014 Jul;165(1):36-41.e1. doi: 10.1016/j.jpeds.2014.01.060. Epub 2014 Mar 17.


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]).

Study design: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Bilirubin / blood*
  • Female
  • Genetic Variation / genetics*
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Humans
  • Hyperbilirubinemia, Neonatal / genetics*
  • Infant, Newborn
  • Jaundice, Neonatal / genetics*
  • Male
  • Milk, Human*
  • Polymerase Chain Reaction


  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Bilirubin