Effects Of UGT1A1 Gene Mutation Sites On Biochemical Indexes Of Patients With Indirect Elevation Of Bilirubin

Background Uridine diphosphate glucuronic acid transferase 1A1(UGT1A1)is a key liver enzyme involved in bilirubin binding and metabolism.UGT1A1 gene mutations can lead to the transcription and translation levels drop,the product is reduced,the activity of UGT1A1 reduce or lose,result in different levels of bilirubin metabolism disorders,causing Crigler-Najjar syndrome type 1,Crigler-Najjar syndrome type 2,Gilbert’s syndrome,and congenital familial nonhemolytic hyperbilirubinemia neonatal jaundice.This paper aims to conduct genotype analysis on patients with elevated serum bilirubin(mainly indirect bilirubin),and further study the influence of different mutation sites of UGT1A1 gene on biochemical indexes of patients with elevated serum bilirubin,which is helpful to understand the genetic basis of different bilirubin levels in patients and assist in diagnosis.Methods In this prospective study,human genome DNA was extracted from 87 patients with elevated serum bilirubin(mainly indirect bilirubin).The target fragments of exon 1,exon 2,3,4 and its intermediate intron,exon 5 and the TATA box of UGT1A1 gene were amplified and genotypes were analyzed,and the effects of different mutation sites of UGT1A1 gene on biochemical indexes of patients with elevated serum bilirubin were further studied.Results Of the 87 patients(59 males and 28 females),65 had only one mutation site,17 had two,and 3 had three.The mutations of promoter TATA-box were:A(TA)6TAA/A(TA)7TAA,(TA)6/7;(TA)7/7.Other mutations occur in exon 1(c.189C>T,c.211G>A,c.686C>A)and exon 5(c.1456T>G).There were no statistically significant differences in the biochemical indexes of TBIL,DBIL,IBIL,ALB,ALT,AST,WBC,N,RBC,HB and PLT between A(TA)7TAA heterozygous mutation and homozygous mutation groups(P>0.05).At the same time,there was no significant difference in gender and age between the two groups(P>0.05).There were no statistical differences in biochemical parameters between patients with one mutation site and patients with two or more mutations,A(TA)7TAA mutation,exon single mutation,TATA box plus other exon mutations.The mutation frequency of c.211G>A was higher in GS patients with serum bilirubin level ≤51μmol/L(P=0.01),while the mutation frequency of c.1456T>G was higher in GS patients with serum bilirubin level > 51μmol/L(P=0.01).Conclusion UGT1A1 gene variation was the main reason for the elevation of unbound bilirubin,and the variation was mainly in the TATA box,exon 1 and 5 regions.GS is an autosomal dominant genetic disease.The homozygous and heterozygous mutations of UGT1A1 have no correlation with bilirubin levels,the c.211G>A and c.1456T>G mutation site had significant difference in bilirubin effect.