Correlation Between UGT1A1 Gene Polymorphism And Neonatal Unexplained Hyperbilirubinemia

Objective: To investigate the association between bilirubin-uridine diphosphate glucuronyl transferase 1A1(UGT1A1)gene polymorphism and neonatal unexplained hyperbilirubinemia.Methods:142 patients with unexplained high unconjugated bilirubinemia admitted to the full-term newborn ward of our hospital(Hunan area)were selected as observation group.71 patients with no hyperbilirubinemia in the same period were randomly selected as the control group.All subjects(n=213 cases)collected venous blood,extracted genomic DNA,PCR amplified the UGT1A1 gene promoter,exon and some intron regions,then sequenced them.The allele frequencies of UGT1A1 gene c.211G>A,c.1091C>T and TATA box mutations were compared between the two groups.According to the results of gene sequencing,patients in the observation group were further divided into different groups,then compare the peak of serum total bilirubin among each group.Results: 1.General information:There was no significant difference in gender,gestational age,hospital admission weight,birth weight,breast-feeding status,alanine aminotransferase and aspartate aminotransferase between the two groups(P >0.05).The data of the two groups were comparable.2.UGT1A1 gene polymorphism in two groups: in the observation group of 142 children,39 cases had no gene mutation,90 cases had single site mutation and 13 cases had compound mutation,the total mutation rate was 72.54%,c.211 G > A,c.1091 C > T and TATA box mutations were more common,the total mutation rates were 57.04%,11.97% and 7.75% respectively.There were 71 cases in the control group,61 cases without gene mutation and 10 cases with single site mutation,the total mutation rate was 14.09%,including only 211G>A and TATA box mutations,the total mutation rates were 11.27% and 2.82%,respectively.3.Comparison of allele frequencies of UGT1A1 gene c.211G>A mutation between the two groups: the c.211G>A mutation frequency of UGT1A1 gene in the observation group and the control group were 38.35% and 5.63%,respectively.The difference between the two groups was statistically significant(P < 0.05).4.Comparison of allele frequencies of UGT1A1 gene c.1091C>T mutation between the two groups: the c.1091C>T mutation frequency of UGT1A1 gene in the observation group was 6.69%,while no c.1091C>T mutation was detected in the control group.The difference between the two groups was statistically significant(P < 0.05).In the 1000 genome database,the gene carrying rate of this locus in the East Asian population was 1.09%,which was statistically significant compared with the observation group(P < 0.05).5.Comparison of allele frequencies of UGT1A1 gene TATA box mutation between the two groups: the TATA box mutation frequency of UGT1A1 gene in the observation group and the control group were 4.58% and 1.41%,respectively.There was no significant difference between the two groups(P > 0.05).6.Comparison of the peak of serum total bilirubin between common mutation sites of UGT1A1 gene in the observation group: The peak of total bilirubin in the c.211G>A mutation group was compared with that in the wild-type group and the TATA box mutation group,the difference was statistically significant(P <0.05).The peak of total bilirubin in the 1091C>T mutant group was compared with that in the wild-type group and the TATA box mutant group,and the difference was statistically significant(P <0.05).There was no significant difference in the peak of total bilirubin between the TATA box mutant group and the wild-type group(P >0.05).Conclusion: UGT1A1 gene c.211G>A,c.1091C>T and TATA box mutations are more common in full-term neonates with unexplained hyperbilirubinemia in in Hunan.The c.211G>A and c.1091C>T mutations are closely related to the occurrence of hyperbilirubinemia in this population,while the TATA box mutation may have no significant correlation with the occurrence of neonatal unexplained hyperbilirubinemia.