Roles of UGT1A1 Gly71Arg and TATA promoter polymorphisms in neonatal hyperbilirubinemia: A meta-analysis.

OBJECTIVE: To identify the association between UGT1A1 Gly71Arg and TATA promoter polymorphisms and neonatal hyperbilirubinemia. METHODS: The studies related to the correlation between UGT1A1 Gly71Arg and TATA promoter polymorphisms and neonatal hyperbilirubinemia were searched systematically in various databases. According to the presence or absence of significant heterogeneity, a random-effect or fixed-effect model was chosen to estimate the overall odds rations (ORs) and 95% confidence intervals (CIs). RESULTS: Totally 21 studies on Gly71Arg polymorphism including 4738 neonates and 13 studies on TATA promoter polymorphism involving 2841 neonates were identified. Significant associations were presented between Gly71Arg polymorphism and neonatal hyperbilirubinemia in Asia [A vs. G, OR(95%CI): 2.327(1.904-2.845), P < 0.001; AA + GA vs. GG, OR(95%CI): 2.253(1.954-2.598), P < 0.001; AA vs. GG + GA, OR(95%CI): 5.166(3.520-7.564), P < 0.001; AA vs. GG, OR(95%CI): 6.458(4.376-9.531), P < 0.001; GA vs. GG, OR(95%CI): 1.920(1.654-2.228), P < 0.001] and Africa [A vs. G, OR(95% CI): 9.750(1.214-78.301), P = 0.032; AA + GA vs. GG, OR(95% CI): 11.000(1.290-93.832), P = 0.028; GA vs. GG, OR(95% CI): 10.000(1.163-85.998), P = 0.036]. TATA promoter polymorphism was associated with an increased risk of neonatal hyperbilirubinemia in Asia [TA7/7 vs. TA6/6 + TA6/7, OR(95%CI): 1.670(1.034-2.696), P = 0.036] and Europe [TA7/7 vs. TA6/6 + TA6/7, OR(95%CI): 2.627(1.722-4.008), P < 0.001]. CONCLUSION: The risk of neonatal hyperbilirubinemia may be increased by the variation of UGT1A1 Gly71Arg in Asia and Africa, as well as the variation of UGT1A1 TATA promoter in Asia and Europe.

Correlation between UGT1A1 polymorphism and neonatal hyperbilirubinemia of neonates in Wuhan.

This study attempts to discuss the correlation between UGT1A1*28 as uridine diphosphate glucuronosyltransferase gene promoter and coding region Gly71Arg gene polymorphism with neonatal hyperbilirubinemia of neonates in Wuhan. A total of 168 neonates were divided into the hyperbilirubinemia group (case group, n=108) and healthy neonates group (control group, n=60). Their DNA was obtained through blood extraction. The gene exon mutation of UGT1A1 was detected by Sanger sequencing, which revealed the relationship between UGT1A1*28 and Gly71Arg polymorphism with neonatal hyperbilirubinemia of neonates. The results showed that: (1) The frequency of UGT1A1*28 allele mutation in the case group and the control group was 9.3% and 10% respectively, with the difference being not significant between the two groups (P>0.05). (2) The frequency of Gly71Arg allele mutation in the case group and the control group was 35.1% and 21.7% respectively, with the difference being significant between the two groups (P<0.01). (3) The serum bilirubin level of Gly71Arg mutant homozygous and heterozygous subgroups (n=66) in the case group was 302.7±31.4 µmol/L, which was significantly higher than 267.3±28.5 µmol/L of the wild subgroup (n=42) (P<0.01). It was suggested that the occurrence of neonatal hyperbilirubinemia of neonates in Wuhan was not associated with UGT1A1*28 gene polymorphism, but closely with the Gly71Arg gene polymorphism. Meanwhile, the Arg allele mutation was related to the degree of jaundice.

Correlation between UGT1A1 Polymorphism and Neonatal Hyperbilirubinemia of Neonates in Wuhan / 华中科技大学学报（医学）（英德文版）

This study attempts to discuss the correlation between UGT1A1*28 as uridine diphosphate glucuronosyltransferase gene promoter and coding region Gly71Arg gene polymorphism with neonatal hyperbilirubinemia of neonates in Wuhan.A total of 168 neonates were divided into the hyperbilirubinemia group (case group,n=108) and healthy neonates group (control group,n=60).Their DNA was obtained through blood extraction.The gene exon mutation of UGT1A1 was detected by Sanger sequencing,which revealed the relationship between UGT 1A 1*28 and Gly71Arg polymorphism with neonatal hyperbilirubinemia of neonates.The results showed that:(1) The frequency of UGT1Al*28 allele mutation in the case group and the control group was 9.3％ and 10％ respectively,with the difference being not significant between the two groups (P＞0.05).(2) The frequency of Gly71Arg allele mutation in the case group and the control group was 35.1％ and 21.7％ respectively,with the difference being significant between the two groups (P＜0.01).(3) The serum bilirubin level of Gly71Arg mutant homozygous and heterozygous subgroups (n=66) in the case group was 302.7±31.4 μmol/L,which was significantly higher than 267.3±28.5 μmol/L of the wild subgroup (n=42) (P＜0.01).It was suggested that the occurrence of neonatal hyperbilirubinemia of neonates in Wuhan was not associated with UGT 1A1*28 gene polymorphism,but closely with the Gly71Arg gene polymorphism.Meanwhile,the Arg allele mutation was related to the degree of jaundice.

The relationship between Gly71Arg and TATA box polymorphism of UGT1A1 gene and prolonged hyperbilirubinemia of breast milk feeding infant in Korean / 소아과

PURPOSE: It has been known that breast milk cause prolonged unconjugated hyperbilirubinemia. UGT1A1 is a important gene of uridine diphosphate glucuronosyltransferase (UGT) which has a major role of bilirubin metabolism. These findings suggest that there is a relationship between UGT1A1 gene mutation and prolonged jaundice of breast feeding infant. The aim of study was to investigate whether a polymorphism of the UGT1A1 gene exist in prolonged hyperbilirubinemia of breast milk feeding Korean infant. METHODS: The genomic DNA was isolated from 50 full term Korean neonates, who had greater than a 10 mg/dL of serem bilirubin after 2 weeks of birth with no significant cause, and the other genomic DNA was isolated from 162 full term Korean neonates of the control population. Both group fed breast milk. We performed direct sequencing of TATA box and Gly71Arg polymorphism of the UGT1A1 gene. RESULTS: Two of the 50 neonates with hyperbilirubinemia had AA polymorphism, and 40 had GA polymorphism. Five of the 129 neonates of the control group had AA polymorphism, and 4 had GA polymorphism. The allele frequency of G>A polymorphism in the hyperbilirubinemia group was 44.0%; it was significantly higher than 5.4% of the control group. TATA box polymorpism was not different both group significantly. CONCLUSION: Our result indicated that Gly71Arg polymorphism is associated with the prolonged hyperbilirubinemia of breast milk-feeding infant in Korean, while TATA box polymorphism is not associated with the prolonged hyperbilirubinemia of breast milk-feeding infant in Korean.