Quantitative trait analysis of polymorphisms in two bilirubin metabolism enzymes to physiologic bilirubin levels in Chinese newborns

J Pediatr. 2014 Dec;165(6):1154-1160.e1. doi: 10.1016/j.jpeds.2014.08.041. Epub 2014 Sep 26.


Objective: To explore the effects of variants in Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) and Heme Oxygenase-1 (HMOX1) on daily physiological bilirubin levels and bilirubin changes during the first week after birth in Chinese newborns. Both UGT1A1 and HMOX1 code rate-limiting enzymes in the bilirubin metabolism pathway.

Study design: We conducted a retrospective quantitative trait study to analyze 4154 daily bilirubin values, 3129 bilirubin changes, and 11 polymorphisms of 988 newborns during the natural course of physiological hyperbilirubinemia.

Results: For UGT1A1, we found minor allele A of rs4148323 (G211A, UGT1A1*6) contributed to higher daily bilirubin levels on days 4-6 (with contributions to variations increasing from 4.8% to 12.3%), minor allele T of rs887829 (c-364t) contributed to lower daily bilirubin levels for days 6 and 7 (with contributions to variations increasing from 7.0% to 10.2%) (P < .03 for all). In addition, minor alleles of rs887829 and (TA)n repeat (UGT1A1*28), and haplotype T-long-G at rs887829-(TA)n-rs4148323 were associated with a decrease in bilirubin levels from day 5 to day 6 (P < .01 for all). No contribution from HMOX1 was found.

Conclusion: Bilirubin levels and changes during the middle and late parts of the first week were attributed to variants and haplotypes in UGT1A1. This quantitative trait study may provide a more robust statistical method for determining the association of genetic factors and bilirubin kinetics to predict the development of neonatal bilirubin in early postnatal life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Bilirubin / metabolism*
  • Female
  • Genetic Variation
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Haplotypes
  • Heme Oxygenase-1 / genetics*
  • Humans
  • Infant, Newborn
  • Jaundice, Neonatal / genetics*
  • Male
  • Retrospective Studies


  • HMOX1 protein, human
  • Heme Oxygenase-1
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Bilirubin