Influence of UGT1A1 Genetic Variants on Free Bilirubin Levels in Japanese Newborns: A Preliminary Study

Int J Environ Res Public Health. 2022 Oct 12;19(20):13090. doi: 10.3390/ijerph192013090.

Abstract

Background: Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two UGT1A1 genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between UGT1A1 variants and Bf levels in newborns has not been elucidated.

Methods: We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two UGT1A1 genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, n = 77) and a non-high Bf group (Bf < 1.0 µg/dL, n = 407), based on the peak Bf values. Logistic regression analysis was performed to calculate the odds ratios (ORs) for each variant allele compared to wild-type alleles.

Results: The frequencies of the A allele in rs4148323 and (TA)7 allele in rs3064744 in the high Bf group (29% and 4%, respectively) were significantly different from those in the non-high Bf group (16% and 12%, respectively). In logistic regression analysis, for rs4148323, the A allele was significantly associated with an increased risk of hyper-free bilirubinemia over the G allele (adjusted OR: 1.80, 95% confidence interval [CI]: 1.19-2.72, p < 0.01). However, for rs3064744, the (TA)7 allele was significantly associated with a decreased risk of hyper-free bilirubinemia over the (TA)6 allele (adjusted OR: 0.42, 95% CI: 0.18-0.95, p = 0.04).

Conclusions: This study is the first to show that the A allele in rs4148323 is a risk factor and that the (TA)7 allele in rs3064744 is a protective factor for developing hyper-free bilirubinemia in Japanese newborns.

Keywords: bilirubin encephalopathy; free bilirubin; genetic variants; hyper-free bilirubinemia; uridine diphosphate glucuronosyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Bilirubin / analysis
  • Genotype
  • Glucuronosyltransferase* / genetics
  • Humans
  • Hyperbilirubinemia, Neonatal* / genetics
  • Infant
  • Infant, Newborn
  • Japan
  • Retrospective Studies

Substances

  • Bilirubin
  • Glucuronosyltransferase
  • UGT1A1 enzyme