Effects of Gly71Arg mutation in UGT1A1 gene on neonatal hyperbilirubinemia: a systematic review and meta-analysis

Chen

The Kaohsiung J of Med Scie

2022

In the Asian general population, at least six single‐nucleotide variants (SNVs) in the UDP‐glucuronosyltransferase (UGT) 1A1 gene have been identified: −3279T>G, −53A(TA)6TAA>A(TA)7TAA, 211G>A, 686C>A, 1091C>T, and 1456T>G. Each of these six SNVs was observed in at least four ethnic groups of the 12 Asian populations studied. In East Asian populations, the descending frequency of these six SNVs was as follows: −3279G>[−53A(TA)7TAA, 211A]>(686A, 1091T)>1456G. Because of the presence of linkage disequilibrium and the expulsion phenomenon, when the SNVs −3279G, −53A(TA)7TAA, 211A, and 686A were simultaneously involved, 15 instead of the estimated 81 genotypes were observed. Those carrying 686AA or 1456GG developed Gilbert's syndrome or Crigler–Najjar syndrome type 2. Both −53A(TA)7TAA/A(TA)7TAA and 211AA are the main causes of Gilbert's syndrome in East Asian populations. In East Asian populations, the 211AA genotype is the main cause of neonatal hyperbilirubinemia, whereas −53A(TA)7TAA/A(TA)7TAA exerts a protective effect on hyperbilirubinemia development in neonates fed with breast milk. Both 211A and −53A(TA)7TAA are significantly associated with adverse drug reactions induced by irinotecan (one of the most widely used anticancer agents) in Asians. However, at least three common SNVs (−3279G, −53A(TA)7TAA, and 211A) should be comprehensively analyzed. This study investigated the clinical significance of these six SNVs and demonstrated that examining UGT1A1 variants in Asian populations is considerably challenging.

Section: Neonatal Hyperbilirubinemiasupporting

confidence: 84%

Bilirubin metabolism and UDP‐glucuronosyltransferase 1A1 variants in Asians: Pathogenic implications and therapeutic response

Chen

The Kaohsiung J of Med Scie

2022

“…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.…”

Section: Introductionmentioning

confidence: 99%

Profiling of UGT1A16, UGT1A160, UGT1A193, and UGT1A128 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing

et al. 2019

Background: Single nucleotide polymorphism (SNP) variants of the uridine diphosphate glucuronosyltransferase 1A1 ( UGT1A1 ) gene have been studied as an important factor in neonatal hyperbilirubinemia (jaundice) severity. Specific ethnicities, including Asians, have certain SNPs that appear more frequently than others. Aim: To identify the most common SNPs in Indonesian neonates and their association with the severity of neonatal hyperbilirubinemia. Methods: Eighty-eight inborn and outborn jaundiced infants from three different hospitals (Bengkulu, Jakarta, Biak Papua) across Indonesia were enrolled in this cross-sectional study and their peak total serum bilirubin (TSB) levels assessed. SNP variant analyses of the TATAA box, promoter, and exon 1 regions of UGT1A1 gene from 78 of the 88 infants were carried out using the SNaPshot R Multiplex Polymerase Chain Reaction (PCR) System followed by DNA sequencing. Results: We detected SNP variants UGT1A1 * 28, UGT1A1 * 60, UGT1A1 * 93 , and UGT1A1 * 6 in our population. Mean total serum bilirubin (TSB) was 14.59 ± 5.57 mg/dL. Bivariate analyses using delivery location, gestational age, birth weight, mother's age, and ethnicity were shown to be associated with moderate-to-severe hyperbilirubinemia ( p < 0.05). None of the four SNPs appeared to be associated with moderate-to-severe hyperbilirubinemia. In multivariate analysis, however, only the “other ethnic group” (e.g., Chinese, Bengkulu, Papua, Bima) category showed an association with moderate-to-severe hyperbilirubinemia, with an odds ratio of 6.49 (95% CI 1.01–41.67; p < 0.05). Conclusions: We found that the UGT1A1 * 60 is the most common SNP detected in neonates with hyperbilirubinemia in the Indonesian population. Interestingly, in Indonesia, UGT1A1 polymorphisms do not appear to be associated with differences in the severity of hyperbilirubinemia.

“…Our results reveal that neonatal hyperbilirubinemia in Taiwanese is related to 211 G > A variant in the UGT1A1 gene, while such a variant is very rare in Caucasians. 6 Therefore, we recommend that information about neonatal hyperbilirubinemia and breastfeeding hyperbilirubinemia could be incorporated into prenatal education for mothers who intend to breastfeed, as other Taiwanese authors reported recently. 26 Furthermore, we agree that further study may be needed to target women who stopped breastfeeding because of breastfeeding hyperbilirubinemia specifically.…”

Section: Discussionmentioning

confidence: 86%

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

Pediatrics & Neonatology

Lin

Liu

et al. 2020