biostudies-literatureHanafusa HJSPS KAKENHIJapan Society for the Promotion of Science13090https://www.ebi.ac.uk/biostudies/studies/S-EPMC9603041biostudies-literatureUnknown19(20)<h4>Background</h4>Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two <i>UGT1A1</i> genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between <i>UGT1A1</i> variants and Bf levels in newborns has not been elucidated.<h4>Methods</h4>We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two <i>UGT1A1</i> genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, <i>n</i> = 77) and a non-high Bf group (Bf < 1.0 µg/dL, <i>n</i> = 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.<h4>Results</h4>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, <i>p</i> < 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, <i>p</i> = 0.04).<h4>Conclusions</h4>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.International journal of environmental research and public healthInfluence of <i>UGT1A1</i> Genetic Variants on Free Bilirubin Levels in Japanese Newborns: A Preliminary Study.PMC960304121K1588020H0010220K08229Ohyama SAbe SKyono YTanimura KNozu KHanafusa HNakasone RFujioka KKido TAshina MfalseInfluence of <i>UGT1A1</i> Genetic Variants on Free Bilirubin Levels in Japanese Newborns: A Preliminary Study.<h4>Background</h4>Free bilirubin (Bf) is a better marker than total serum bilirubin (TSB) for predicting bilirubin encephalopathy (BE). To date, two <i>UGT1A1</i> genetic variants (rs4148323 and rs3064744) have been associated with neonatal hyperbilirubinemia; however, the direct association between <i>UGT1A1</i> variants and Bf levels in newborns has not been elucidated.<h4>Methods</h4>We retrospectively analyzed the clinical data of 484 infants, including the genotype data of two <i>UGT1A1</i> genetic variants. We divided the infants into a high Bf group (Bf ≥ 1.0 µg/dL, <i>n</i> = 77) and a non-high Bf group (Bf < 1.0 µg/dL, <i>n</i> = 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.<h4>Results</h4>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, <i>p</i> < 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, <i>p</i> = 0.04).<h4>Conclusions</h4>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.2022-01-01T00:00:00Z2022 Oct2026-04-08T18:25:26.731Z2025-04-19T04:20:45.185ZS-EPMC96030413629367110.3390/ijerph192013090