Neonatal Hyperbilirubinemia UGT1A1 Gene Polymorphism And Correlation Analysis

Objective: To investigate the features of neonatal hyperbilirubinemia UGT1A1 gene polymorphism in Shanghai area and the corresponding level of bilirubin based on 92 cases of unexplained neonatal hyperbilirubinemia uridine diphosphate glucuronic acid transferase(UGT1A1)polymorphism analysis and explore the relationship between UGT1A1 gene mutation and neonatal hyperbilirubinemia in Shanghai area.Methods: Neonates of Chinese Han population with neonatal hyperbilirubinemia admitted to our department from April 2015 to December 2016 were reviewed.After excluding these diseases:premature birth,asphyxia,low birth weight,low temperature,dehydration,acidosis,hypoalbuminemia albumin(less than 30 g/L),hemolytic disease of the newborn,G6 PD deficiency,infections,other liver diseases and congenital diseases,peripheral venous blood was collected for UGT1A1 gene sequencing with Sequencher software.The locations and types of mutation were observed.Meanwhile,Bilirubin level of cases was collected when they were admitted to hospital.And according to theserum bilirubin level cases were divided into serious high cholesterol group and ordinary high cholesterol group,both were the case group,the control group was the same period without jaundice or TSB remained in the physiological jaundice level of the newborn,and the frequency of the UGT1A1 gene polymorphism in the control group was derived from the Chinese population data in the thousand people genome database.To compare the UGT1A1 genotype,Gly71 Arg genotype and allele frequency difference between the two groups,and to observe the type of UGT1A1 gene mutation and the corresponding bilirubin levels in different cases.Results(1)According to the bilirubin level in neonates were divided into case group and observation group,92 cases,the observation group had 90 cases,between the two groups in age,birth weight,albumin,there was no significant difference of alanine aminotransferase(P>0.05),total bilirubin level differences between the two groups had statistical significance(P<0.05).(2)UGT1A1 genes of 92 cases who conform to the conditions was sequenced with neonatal peripheral venous blood.There were 76 mutation newborns,and the mutation rate is 82.6%.According to the frequency,there were 34 Gly71 Arg heterozygous mutations(37.0%),18Gly71 Arg homozygous mutations(19.6%),12 multiple mutations(13.0%),7 Pro364 Leu mutations(7.6%),4 TATA promoter insert(4.3%),and 1Pro299 Gln heterozygous mutations(1.1%).Gly71 Arg heterozygous mutations,Pro364 Leu heterozygous mutations and Arg367 His heterozygous mutations were contained in multiple mutations.(3)Comparing the two groups in the UGT1A1 gene Gly71 Arg polymorphism frequency,severe hyperbilirubinemia group and common hyperbilirubinemia group UGT1A1 gene mutation frequency was higher than the control group,the difference was statistically significant(P<0.05),high cholesterol group Gly/Arg+Arg/Arg genotype frequency was 65%,severe hyperbilirubinemia group Gly/Arg+Arg/Arg genotype frequency was 54.1%,there was no significant difference between the two groups(P>0.05);high cholesterol group Arg allele frequency was42.5%,severe hyperbilirubinemia group Arg allele frequency 36.8%,the difference between the two groups was not statistically significant(P>0.05).(4)Peak serum bilirubin of gene mutation type group and wild type group were compared.Each group bilirubin differences were statistically significant(P<0.05).There was no significant difference between each groups in the type of gene mutation and the corresponding peak bilirubin value(P >0.05).Conclusions(1)The mutation of Gly71 Arg gene carrying UGT1A1 gene is related to the formation of neonatal hyperbilirubinemia.(2)High blood bilirubin neonatal with unexplained jaundice has higher UGT1A1 gene mutation rate.And the common types of mutations in the Shanghai area including Gly71 Arg heterozygous and homozygous mutations,Pro364 Leu mutations,TATA promoter inserted.Gly71 Arg is still the hotspot mutation site of UGT1A1 gene in unexplained hyperbilirubinemia.There is certain relevance between different types of genetic mutations and corresponding bilirubin level.(3)Children of wild type groups have higher level of bilirubin,which suggests excluding the UGT1A1 there may be other gene mutations involved in the formation process of high bilirubin.