Abstract
To date, the genetic risk factors for neonatal hyperbilirubinemia remain unknown in Southeastern China. This case-control study aimed to identify the genetic risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China. A total of 286 hyperbilirubinemic newborns were enrolled as a case group, and 250 randomly selected newborns without jaundice or with a bilirubin level that was lower than the threshold required for phototherapy served as controls. The serum levels of total bilirubin, unconjugated bilirubin, and direct bilirubin were measured, and the common genetic loci in UGT1A1, OATP1B1, and HO-1 genes were genotyped. Higher incidence of ABO incompatibility and G6PD deficiency was detected in the case group compared to the control group (P < 0.01). There were significant differences in the frequencies of rs4148323 and rs1805173 genotypes between the case and control groups (P < 0.05). At the rs4148323 locus, the frequencies of GA heterozygotes and AA mutant homozygotes were higher in the case group than in the control group (P < 0.05), and at the rs1805173 locus, the frequencies of LS, MS, and SS genotypes were higher in the case group than in the control group (P < 0.05). A higher frequency of rs4148323 A allele and rs1805173 S allele was detected in the case group compared to the control group (P = 0). Additionally, multivariate logistic regression analysis identified that the mutant genotype of rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and SS genotype at rs1805173 locus of the HO-1 gene were genetic risk factors of neonatal hyperbilirubinemia. Our data demonstrate that G211 mutation in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the repeats in the promoter region of the HO-1 gene are risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China.
Highlights
Hyperbilirubinemia is a common disorder in newborns [1, 2]
This case-control study was designed to examine the associations of ABO incompatibility, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the polymorphisms of the Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), Organic anion transporting polypeptide 1B1 (OATP1B1), and heme oxygenase-1 (HO-1) genes with neonatal hyperbilirubinemia in Southeastern China, and the results of multivariate logistic regression analyses showed that the mutant genotype of rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the (GT)n repeats in the promoter region of the HO-1 gene were genetic risk factors for neonatal hyperbilirubinemia in Southeastern China
In a prospective case-control study to assess the association between HO-1 gene variants and hyperbilirubinemia risk in Indian newborns, the incidence of short (GT)n allele (≤ 20) was three times higher in hyperbilirubinemic neonates than in controls, and short (GT)n repeats of HO-1 gene were identified as an independent risk factor for neonatal hyperbilirubinemia (OR = 4.4, 95% CI = 1.2–16.8) [14]
Summary
Hyperbilirubinemia is a common disorder in newborns [1, 2]. Severe hyperbilirubinemia may cause bilirubin encephalopathy, and even the survivors may develop chronic or permanent damage and sequelae in the nervous system [3,4,5]. The exact pathogenesis of neonatal hyperbilirubinemia has not been fully understood, perinatal and genetic factors are widely accepted to jointly contribute to this disorder [6,7,8]. It has been shown that the short (GT)n allele in the promoter region of the HO-1 gene may affect HO1 transcription, and the number of (GT)n alleles negatively correlates to HO-1 transcription, while short (GT)n repeats may cause an increase in the HO-1 transcription, resulting in enhancement of heme catabolism and an increase in the heme production [9]. Uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) is an important metabolic enzyme
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
