Clinical Significance of UGT1A1 Genetic Analysis in Chinese Neonates with Severe Hyperbilirubinemia

Neonatal hyperbilirubinemia is common in Asia, and the importance of genetically determined conditions has been recently recognized. The aim of this study was to assess the clinical utility of genetic testing in Chinese neonates with severe hyperbilirubinemia.Fifty-eight term infants with bilirubin level ≥ 20 mg/dL (342 μmol/L), and 65 controls were enrolled in the study. Variation status of UGT1A1, G6PD, and thalassemia genes in our study cohort was determined by direct sequencing or genotype assays.Among these case infants, seven were confirmed with G6PD deficiency, four were heterozygous for α- or β-thalassemia, and forty-four were detected with at least one heterozygous UGT1A1 functional variant, including nine homozygous for UGT1A1 variation. As well as the predominant c.211G>A (Gly71Arg) variant, three UGT1A1 coding variants [c.1091C>T (Pro364Leu), c.1352C>T (pro451leu), and c.1456C>T (Tyr486Asp)] were observed in our case neonates. The results of multivariate logistic regressions, adjusted for covariates, revealed odds ratios for neonates who carried heterozygous, homozygous variation at nucleotide 211 of UGT1A1, and G6PD deficiency of 3.47 (1.26-9.55), 12.46 (1.09-142.7) ,and 12.87 (1.32-135.87) compared with those having the wild genotype and normal G6PD activity, respectively.Besides G6PD-deficiency screening, UGT1A1 genetic analysis, and especially the UGT1A1*6(c.211G>A, p.Arg71Gly) polymorphism detection, may be taken into consideration for early diagnosis and treatment of severe hyperbilirubinemic newborns in southern China.