The Ugt1a1 Gene Mutation And Umbilical Cord Blood Bilirubin Levels And Neonatal Jaundice Related Research

Introductionneonatal hyperbilirubinemia is a common problem faced by the pediatricians in world wide. Up to now many factors which cause neonatal hyperbilirubinemia have been discovered, however, there are still some patients with jaundice that cann't be interpreted by our present knowledge. UDP-glucuronosyl transferase (UGT) plays a critical role in bilirubin conjugation. Defects of this enzyme can cause a nonhemolytic unconjugated hyperbilirubinemia. The major human bilirubin-glucuronidating UGT is UGTIAI. Recent studies have revealed that mutations in the UGTIAI gene may lead to hyperbilirubinemia and prolonged unconjugated hyperbilirubinemia of the newborn. Our present study analysed the relatinship between the polymorphisms in the UGTIAI gene and serum levels of bilirubin incord blood in newborns who were follwed up, in order to explore the initial influence of mutation of UGT1A1gene on neonatal bilirubin metablism and predict development of neonatal hyperbilirubinemia.MethodsThe samples were acquried randomly from the cord blood of 48 full-term healthy newborns. The serum level of bilirubin, liver function and blood cells count were measured. The genomic DNA was isolated from the leukocytes of the cord blood. Exon 1 of the UGT1 A1 gene, and its flanking intronic regions were amplifiedby PCR (polymerase chain reaction).The PCR products were sequenced directly. These newborns were surveilled with transcutaneous bilirubin (TCB) by the age of 24 hours. The serum samples were taken and bilirubin were measured if TCB exhibited abnormal. All newborns were followed up for 2 weeks and the serum bilirubin were monitored.ResultsNineteen of 48 infants had at least 1 UGT1A1 mutation. The identical transition mutation is at nucleotide number 211 in exon 1. The substitution of adenine for guanine changed the codon form GGA toAGA, causing arginine to replace glycine at position 71 of the corresponding protein. There were 15 heterozygous cases and 1 homozygous case. Three accompanied the mutation in other positions at nucleotide number 686Câ†'A; at 845Aâ†'T; at 231Gâ†'A. All of them were heterozygous.Comparing the serum level of bilirubin between the infants with UGT1A1 gene mutation and non- mutation, the former is significant higher than the latter (p<0.05). However, there is no statistic difference between the two groups in Hb, serum GPT, GOT and albumin levers.Infants with UGT1A1 gene mutation have significant higher TCB value than that non-mutation subjects at 48 hours and 96 hours after birth. (p<0.05).Total bilirubin ≥205.2 μ mol/1 within 96 hours after birth or prolonged jaundice were found 8 in UGT1A1 gene mutation group and 3 in normal group (p<0.05).ConclusionsUGT1A1 gene mutation is one of the high risk factors of neonatal jaundice. The hyperbilirubin caused by this gene mutation may manifest as early as in later fetal life.