Bilirubin metabolism-related genetic variants in neonatal hyperbilirubinemia: a multicenter case-control study in northern China
10 affiliations
- 1Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College , ,
- 2Department of Neonatology, Capital Center for Children’s Health, Capital Medical University, Capital Institute of Pediatrics , ,
- 3Laboratory Center, Capital Center for Children’s Health, Capital Medical University, Capital Institute of Pediatrics , ,
- 4Department of Pediatrics, Beijing Chaoyang Hospital, Capital Medical University , ,
- 5Department of Obstetrics, The First Hospital of Tsinghua University, School of Clinical Medicine Tsinghua Medicine Tsinghua University , ,
- 6Neonatal Department, Haidian District Maternal and Child Health Care Hospital , ,
- 7Neonatal Department, Liaoning Maternal and Child Health Hospital , , ,
- 8Neonatal Department, Inner Mongolia Maternity and Child Health Care Hospital Neonatology Division , , ,
- 9Department of Pediatrics, Beijing Aerospace General Hospital , ,
- 10Neonatal Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University , ,
Abstract
Neonatal hyperbilirubinemia (NHB) is common in neonates, and genetic factors are important contributors to bilirubin metabolism. However, data on NHB-related genetic variants in northern China remain limited. This multicenter case-control study included 413 neonates hospitalized with unexplained NHB and 120 control neonates who had not been diagnosed with hyperbilirubinemia at enrollment on the day of birth. Twelve hotspot loci in UGT1A1, G6PD, SLC25A13, SLC10A1, and ABCC2 were genotyped using multicolor melting curve analysis. The overall target variant detection rate was significantly higher in cases than in controls (63.0% vs. 45.0%; OR = 2.08, 95% CI: 1.38–3.13, P < 0.001). UGT1A1 variants were the most frequently detected and were more common in cases than in controls (OR = 2.20, 95% CI: 1.45–3.33, P < 0.001). UGT1A1 c.211G>A was the predominant locus, and carriers of at least one variant allele were more frequent in cases than in controls (53.3% vs. 37.5%; OR = 1.90, 95% CI: 1.25–2.89, P = 0.002), with the association remaining significant after FDR correction. Multi-site variants were detected in 34 cases and 5 controls. Among these neonates, 25 had within-gene multi-site variants, all involving UGT1A1, whereas 14 had cross-gene multi-site variants, mainly involving coexistence of UGT1A1 variants with SLC10A1 or G6PD variants. These findings provide regional data on the distribution of bilirubin metabolism-related genetic variants in northern Chinese neonates with unexplained NHB.
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BibTeX
@article{sheng2026bilirubin,
title = {{Bilirubin metabolism-related genetic variants in neonatal hyperbilirubinemia: a multicenter case-control study in northern China}},
author = {Sihan Sheng and Ying Li and Lijuan Ma and Hesheng Chang and Yanmei Guan and Yanzhe Lei and Chunying Tan and Arigonggaowa and Hongfei Wen and Chen Kou and Yajuan Wang},
journal = {Frontiers in pediatrics},
year = {2026},
month = oct,
doi = {10.3389/fped.2026.1945311},
url = {https://europepmc.org/article/PMC/PMC13727740},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bilirubin metabolism-related genetic variants in neonatal hyperbilirubinemia: a multicenter case-control study in northern China
AU - Sihan Sheng
AU - Ying Li
AU - Lijuan Ma
AU - Hesheng Chang
AU - Yanmei Guan
AU - Yanzhe Lei
AU - Chunying Tan
AU - Arigonggaowa
AU - Hongfei Wen
AU - Chen Kou
AU - Yajuan Wang
PY - 2026
DA - 2026/10/20
JO - Frontiers in pediatrics
DO - 10.3389/fped.2026.1945311
UR - https://europepmc.org/article/PMC/PMC13727740
AB - Neonatal hyperbilirubinemia (NHB) is common in neonates, and genetic factors are important contributors to bilirubin metabolism. However, data on NHB-related genetic variants in northern China remain limited. This multicenter case-control study included 413 neonates hospitalized with unexplained NHB and 120 control neonates who had not been diagnosed with hyperbilirubinemia at enrollment on the day of birth. Twelve hotspot loci in UGT1A1, G6PD, SLC25A13, SLC10A1, and ABCC2 were genotyped using multicolor melting curve analysis. The overall target variant detection rate was significantly higher in cases than in controls (63.0% vs. 45.0%; OR = 2.08, 95% CI: 1.38–3.13, P < 0.001). UGT1A1 variants were the most frequently detected and were more common in cases than in controls (OR = 2.20, 95% CI: 1.45–3.33, P < 0.001). UGT1A1 c.211G>A was the predominant locus, and carriers of at least one variant allele were more frequent in cases than in controls (53.3% vs. 37.5%; OR = 1.90, 95% CI: 1.25–2.89, P = 0.002), with the association remaining significant after FDR correction. Multi-site variants were detected in 34 cases and 5 controls. Among these neonates, 25 had within-gene multi-site variants, all involving UGT1A1, whereas 14 had cross-gene multi-site variants, mainly involving coexistence of UGT1A1 variants with SLC10A1 or G6PD variants. These findings provide regional data on the distribution of bilirubin metabolism-related genetic variants in northern Chinese neonates with unexplained NHB.
SN - 2296-2360
ER -