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

BACKGROUND

Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between 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 genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, = 77) and a non-high Bf group (Bf < 1.0 µg/dL, = 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) 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, < 0.01). However, for rs3064744, the (TA) allele was significantly associated with a decreased risk of hyper-free bilirubinemia over the (TA) allele (adjusted OR: 0.42, 95% CI: 0.18-0.95, = 0.04).

CONCLUSIONS

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