Genetic Association Between Hyperbilirubinemia And UGT1A1 Polymorphism In Vietnamese Newborns

Background:Jaundice,also known as icter,is one of the most common neonatal problems.It has been found that unconjugated bilirubin functions through the key enzymes of UDP in the liver,and is conjugated with glucuronic acid to form conjugated bilirubin,which is then excreted through a series of complex processes.In recent years,more and more attention has been paid to the study of UGTIAI gene mutation leading to decreased enzyme activity or defect causing hyperbilirubinemia.The polymorphisms of different UGT1A1 gene promoters and coding regions will lead to the decrease of UGTIAI gene expression or enzyme activity.Studies have shown that the most common polymorphism of UGTIAI gene in Caucasians is the insertion mutation,that is,the insertion of an extra TA into the normal sequence A(TA)6TAA of the promoter TATA box,known as UGT1A1*28,which means that(TA)6TAA becomes(TA)7TAA.Among Asians population,the most common type of mutation are missense mutations of the first exon,especially UGTIA1*6 G211A(Gly71Arg,G71R).G71R mutation,that is exon 211 nucleotide G was replaced by A in UGTIAI gene,resulting in Gly being replaced by Arg.Thus,there were significant differences in UGTIAI gene mutation sites related to neonatal hyperbilirubinemia between different ethnic groups.The socialist republic of Vietnam(Vietnam)is located in the east of the indo-china peninsula in southeast Asia,borders on Guangxi in the north and also is the newborn jaundice high incidence area.Currently,there are no reports on the relationship between UGT1A1 gene mutation and neonatal hyperbilirubinemia in Vietnam.It is not clear whether there are differences in the polymorphic frequency of UGT1A1 in neonates with hyperbilirubinemia in Vietnam and other countries.This study was carried out and the results are reported as follows.Objective:To investigate the relationship between newborn jaundice of Vietnam population and the polymorphism of the promoter TATA box and the first exon of bilirubin uridine diphosphateglucuronosyl transferase(UGT1A1).Methor:A total of 149 neonates were divided into the hyperbilirubinemia group(case group,n=99)and Non-jaundice group(control group,n=50).The gene exon mutation of UGT1A1 in the two groups were detected by PCR and direct sequencing,which revealed the relationship between UGT1A1 polymorphism with neonatal hyperbilirubinemia of neonates.The types of UGT1A1 mutation in the case group and the total serum bilirubin(TSB)levels with different genotypes were observedResults:(1)The detected mutation frequency ranged from high row to low row,respectively:among 149 neonates,there were 51(34,23%)mutations of c.211G>A.The(TA)7 mutation of TATA box has 14 case(9,4%);c.189C>T mutation has 5 case(3,36%);c.190G>A mutation has 1 case(0.7%);c.378C>T mutation has 1 case(0.7%)and c.686C>A mutation was also 1 case(0.7%).(2)The frequency of c.211G>A(UGT1A1*6)allele mutation in the case group and the control group was 27.3%and 5.0%,respectively,with the difference being significant between the two groups(P<0.01).The frequency of(TA)7(UGT1A1*28)allele mutation in the case group and the control group was 5.1%and 6.0%,respectively,with the difference being not significant between the two groups(P>0.01).The frequency of c.189C>T allele mutation in the case group and the control group was 2.5%and 0%,respectively,with the difference being not significant between the two groups(P>0.01)(3)In the case group,the TSB level of G71R homozygous children patients was higher than that of the wild type and heterozygous children(all P<0.01).Conclusions:The variation of UGT1A1 coding sequence 211 G>A is a hotspot mutations of unconjured hyperbilirubinemia in Vietnamese neonates.The UGT1A1 211G>A mutation is not only associated with the risk of unconjured hyperbilirubinemia in Vietnamese neonates,but also positively correlated with the severity of hyperbilirubinemia.