Association between UGT-1A1 gene GLY71Arg polymorphism and severe unexplained indirect hyperbilirubinemia among neonates

Abstract

Background Neonatal jaundice is considered the most prevailing clinical health problem among neonates. Numerous etiological factors are responsible for the development of pathological neonatal jaundice. Almost half of the cases have no well-identified risk factor suggesting an underlying genetic risk. Aim We aimed at investigating the relation between uridyl-diphosphate-glucuronosyltransferase 1A1 (UGT-1A1) gene Gly71Arg (G71R) polymorphism and the occurrence of unexplained severe indirect hyperbilirubinemia among Egyptian neonates. Patients and methods A case–control study was conducted on 81 term neonates presented with serum total bilirubin greater than or equal to 17 mg/dl with no identified underlying cause. Eighty-one age-matched and sex-matched term neonates without clinical jaundice were taken as controls. All neonates (cases and controls) were genotyped for the presence of UGT-1A1 gene G71R polymorphism using PCR restriction fragment length polymorphism. Neonatal cases were classified according to serum total bilirubin into four classes of severity: significant, severe, extreme, and hazardous hyperbilirubinemia. Results Genotype distribution frequency for G71R polymorphism was in accordance with Hardy–Weinberg equilibrium among controls but not among cases. There was significant increase in G71R A/G 50 (61.7%), A/A six (7.4%) genotypes, and A 62 (38.3%) allele distribution among cases with significant increase in estimated risk of unexplained hyperbilirubinemia with odds ratio (95% confidence interval) and P value of 8.6 (4.14–18.14) and P=0.000, 15.5 (1.78–136.2) and P=0.001, and 5.28 (2.92–9.57) and P=0.000, respectively when compared with controls. Significantly higher levels of total bilirubin among jaundiced neonates were observed with the A/A genotype followed by te A/G genotype as compared with the G/G wild genotype (P=0.000). Moreover, a significant association was found between the distribution of G71R genotypes and severity of jaundice. Conclusion UTG-1A1 gene G71R A/G, A/A genotypes, and A allele were associated with significant increased risk of severe unexplained indirect hyperbilirubinemia among Egyptian neonates.