Correlation between UGT1A1 polymorphism and neonatal hyperbilirubinemia of neonates in Wuhan

Abstract

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.

Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing

“…Heterozygous forms display 60% lower activity, while the activity in homozygous forms is even less at <35%. Whereas, the presence of UGT1A1 * 6 is known to be a risk factor for mild adult hyperbilirubinemia (GS) in Caucasian and East Asian populations (16, 19, 28, 39), the prevalence of this SNP is low in the Southeast Asian population (17, 23, 28). Our study confirms this with higher occurrence of wild-type UGT1A1 than the UGT1A1 * 6 SNP (90.5 vs. 9.5%) with an OR of 0.72 (0.11–5.36).…”

“…UGT1A1 genetic variants that lead to reduced activity and decreased expression of the enzyme have been shown to be associated with non-hemolytic hyperbilirubinemia syndromes such as Gilbert's syndrome (GS) and Crigler-Najjar's syndrome types I and II (CN I and CN II, respectively) (1, 10–15). A variant of the TATAA box that has an additional TA insertion (A(TA)7TAA) ( UGT1A1 * 28 ) was found to be associated with GS and CNs, with the mutation being found most frequently in Caucasian and African populations (1, 13, 16–19). In the East Asian population, however, UGT1A1 * 6 (211G > A) is the most prevalent single nucleotide polymorphism (SNP) (16, 17, 20, 21).…”

“…A variant of the TATAA box that has an additional TA insertion (A(TA)7TAA) ( UGT1A1 * 28 ) was found to be associated with GS and CNs, with the mutation being found most frequently in Caucasian and African populations (1, 13, 16–19). In the East Asian population, however, UGT1A1 * 6 (211G > A) is the most prevalent single nucleotide polymorphism (SNP) (16, 17, 20, 21). This variant leads to an amino acid substitution of glycine-71 to arginine.…”

Effects of variation status and enzyme activity for UDP-glucuronosyltransferase 1A1 gene on neonatal hyperbilirubinemia

“…Nevertheless, the main findings of our results are in agreement with random studies reported by Japanese and Chinese. 16e18, 20,22,23 Therefore, this study may provide important references for Asian populations. Second, the further factor for the development of hyperbilirubinemia, the variation at nucleotide À3279 (T > G) (UGT1A1)60, rs4124874) in the UGT1A1 gene, 11,25 was ignored.…”

The importance of the UGT1A1 variants in the development of osteopenia and osteoporosis in postmenopausal women

“…In the present study, the frequency of the UGT1A1*28 variant among Caucasian women was assessed. The search for a connection and a possible correlation between the variants of the analyzed gene and various diseases has so far been reported in the literature for neonatal jaundice 24 , and tumors 25 , 26 , among others. In this study, a comparison of the homozygous 6/6 genotype frequency of the UGT1A1*28 variant (rs3064744) between the women with osteopenia and postmenopausal controls revealed no differences.…”