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.