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]).

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.

• Authors: Yoshihiro Maruo, Yoriko Morioka, Hiroshi Fujito, Sayuri Nakahara, Takahide Yanagi, Katsuyuki Matsui, Asami Mori, Hiroshi Sato, Robert H Tukey, Yoshihiro Takeuchi
• Journal: The Journal of pediatrics (J Pediatr) Vol. 165 Issue 1 Pg. 36-41.e1 (Jul 2014) ISSN: 1097-6833 [Electronic] United States
• PMID: 24650397 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• UGT1A1 enzyme
• Glucuronosyltransferase
• Bilirubin

Topics

• 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