UGT1A1 variants contribution to neonatal hyperbilirubinemia: evidence from whole exome sequencing Running title: UGT1A1 variants contribution to neonatal hyperbilirubinemia

Abstract

Abstract Background It is widely recognized that genetic variation is among the risk factors associated with neonatal jaundice. Therefore, the objective of this study was to assess the impact of genetic variants on Chinese neonates with hyperbilirubinemia. Methods This cohort consisted of 43 cases with normal bilirubin levels, 54 cases categorized as the medium jaundice group (total serum bilirubin less than 342 umol/L), and 33 cases belonging to the high jaundice group (total serum bilirubin exceeding 342 umol/L). Whole exome sequencing was performed on the neonates to identify genetic variations. Results UGT1A1-G71R, mixed feeding and breast feeding were significantly correlated with higher bilirubin value. Homozygous SNP of CAPN12, ECT2L, SLC9B2, PLEKHA4, and hemizygous G6PD were only found in jaundice group but not in control group. Consistent with the result of linear regression, feeding pattern and UGT1A1 G71R were all correlated with level of bilirubin in Fisher exact test (p = 7.81E-13, and p = 2.48E-07, respectively). Conclusion The UGT1A1 gene variants emerged as a prominent risk factor for neonatal jaundice, significantly contributing to elevated bilirubin levels in Chinese neonates, particularly in conjunction with breastfeeding.