Association of neonatal hyperbilirubinemia with uridine diphosphate-glucuronosyltransferase 1A1 gene polymorphisms: Meta-analysis

Background: Recent reports have suggested that genetic factors, including mutations in the coding region or promoter of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) may increase the risk of development of neonatal hyperbilirubinemia, but the relationship has not been evaluated on systematic review or meta-analysis. Methods: A meta-analysis of observational studies reporting effect estimates and 95% confidence intervals (95% CI) was conducted on the association between UGT1A1 polymorphisms and neonatal hyperbilirubinemia. Results: A total of 27 eligible studies were identified. In total, 17 studies focused on the association of neonatal hyperbilirubinemia with UGT1A1 Gly71Arg polymorphisms, which indicated that these polymorphisms were associated with an increased risk of neonatal hyperbilirubinemia (A/A+G/A vs G/G: odds ratio [OR], 2.70; P = 0.00; 95% CI: 2.22-3.29; I(2) = 0.0%; P(heterogeneity) = 0.55). Subgroup analyses by ethnicity validated this correlation in Asian, but not in Caucasian, populations (OR, 1.74; P = 0.10; 95% CI: 0.90-3.35; I(2) = 0.00%; P(heterogeneity) = 0.67). Furthermore, 18 studies focused on the association of neonatal hyperbilirubinemia with UGT1A1 TATA promoter polymorphisms. These studies concluded that TATA promoter variants were not associated with an increased risk of neonatal hyperbilirubinemia (7/7 + 6/7 vs 6/6: OR, 1.13; P = 0.23; 95% CI: 0.93-1.37; I(2) = 80.0%; P(heterogeneity) = 0.00). Conclusion: UGT1A1 Gly71Arg polymorphisms are a risk factor for developing neonatal hyperbilirubinemia in Asian, but not Caucasian, subjects. UGT1A1 TATA promoter polymorphisms were not associated with an increased risk of neonatal hyperbilirubinemia in Asian subjects, but results from the Caucasian population were conflicting and require further epidemiological investigation.