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

Wang, Jing; Yin, Jiansong; Xue, Mei; Lyu, Jun; Wan, Yu

doi:10.1016/j.gene.2020.144409

Cited by 18 publications

(16 citation statements)

References 43 publications

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“…To date, more than 150 pathogenic variants of the UGT1A1 gene have been identified,(Steventon, 2020 ) where the most common ones include A(TA) 7 TAA and p.Gly71Arg variants. Our findings showed that A(TA) 7 TAA and p.Gly71Arg variants were also the most common variants in Chinese patients, which is consistent with the findings in other Asian populations (Maruo et al, 2016 ; Sun et al, 2017 ; Wang et al, 2020 ). A(TA) 7 TAA variant is the insertion of an additional TA sequence in the TA repetitive sequence of the original A(TA) 6 TAA sequence in the promoter.…”

Section: Discussionsupporting

confidence: 92%

“…UGT1A1 gene (OMIM#191740), which is responsible for the coding of UDP‐glucuronosyltransferase 1A1 (UGT1A1), contains five exons, while the promoter of the gene contains an A(TA) 6 TAA repetitive sequence that is closely associated with the initiation of gene transcription (Wang et al, 2020 ). UGT1A1 gene is a member of the UGT1A subfamily, which shares four common exons from exon 2 to exon 5 with other members and has a unique exon 1.…”

Section: Introductionmentioning

confidence: 99%

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Genetic testing of UGT1A1 in the diagnosis of Gilbert syndrome: The discovery of seven novel variants in the Chinese population

Han

Zhang

et al. 2022

Molec Gen & Gen Med

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Background Genetic testing of UGT1A1 was used to facilitate the diagnosis of Gilbert syndrome, and analyze the distribution features of pathogenic variants in the Chinese population. Methods DNA was extracted from whole blood samples of patients with unconjugated hyperbilirubinemia, and sequencing of the UGT1A1 gene was performed after PCR amplification. After alignment with reference sequences, the known pathogenic variants were identified, the variant spectrum was analyzed, and the pathogenicity of novel variants was predicted using online mutation prediction tools. Results A total of 117 patients were confirmed with Gilbert syndrome by UGT1A1 genetic diagnosis, where the most common pathogenic variants included promoter A(TA)7TAA insertion and p.Gly71Arg missense variant. Following novel variants were also identified: p.Ala61Gly, p.Tyr67Phe, p.Leu166Alafs*16, p.Arg240Lys, p.Ser306Phe, p.Arg341Gln, and p.Glu424* variants. Conclusions Genetic testing of UGT1A1 in clinical practices could facilitate confirming Gilbert syndrome and performing differential diagnosis. The pathogenic variant spectrum in the Chinese population was similar to other Asian populations. The novel pathogenic variants identified in this study require further investigation.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Genetic testing of UGT1A1 in the diagnosis of Gilbert syndrome: The discovery of seven novel variants in the Chinese population

Han

Zhang

et al. 2022

Molec Gen & Gen Med

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“…(TA) 7 TAA/A(TA) 7 TAA, is the main genetic cause in Asians. 73,74 The results of our review confirmed these findings (except for Indonesian, 14,40 Malaysian, 52 and Saudi 21 populations). Moreover, the TA 7 repeat variant of UGT1A1 appears to exert a protective effect on hyperbilirubinemia development in Chinese, 28 Japanese, 48,75 and Taiwanese 57,67 neonates fed breast milk.…”

Section: Neonatal Hyperbilirubinemiasupporting

confidence: 83%

Bilirubin metabolism andUDP‐glucuronosyltransferase1A1variants in Asians: Pathogenic implications and therapeutic response

Huang

Chen

Huang

2022

The Kaohsiung J of Med Scie

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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.

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“…In addition, the East Asian race is one of the important risk factors for severe hyperbilirubinemia [19] and ETT is still an important clinical treatment of severe neonatal hyperbilirubinemia in mainland China [20,21], but there are relatively few studies on ETT in China. Therefore, in this study, our aim was to investigate the incidence of ETT in the treatment of severe neonatal hyperbilirubinemia in Wuhan.…”

Section: Introductionmentioning

confidence: 99%

A single-center experience on exchange transfusion therapy in 123 full-term cases of severe neonatal hyperbilirubinemia in Wuhan

Duan

Gan

2020

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective: To describe the clinical experience in application of exchange transfusion therapy (ETT) in the treatment of severe neonatal hyperbilirubinemia. Methods: The clinical data and examination results of severe neonatal hyperbilirubinemia fullterm cases treated by ETT were analyzed retrospectively, the etiology and risk factors of severe neonatal hyperbilirubinemia were statistically analyzed, and the statistical characteristics of the children in each etiological group and the incidence of adverse events of ETT were analyzed. Results: The age of jaundice, peak total bilirubin after phototherapy and ETT in 123 full-term infants were 2.0 (1.0, 3.0) days, 4.0 (2.0, 7.0) days and 4.0 (2.0, 7.0) days, respectively, of which 68 were male and 55 were female. The main pathogeny of severe neonatal hyperbilirubinemia was blood group incompatibility hemolytic disease of newborn (HDN). Age of ETT, total bilirubin after ETT, gender and BAEP results were different between ABE and non-ABE infants. Weight loss can be used as a predictor of hospitalization length. The major adverse events related to ETT were hypocalcemia, hypomagnesemia, hyponatremia and thrombocytopenia. Conclusions: ETT can rapidly reduce the level of total bilirubin to prevent ABE and play an important role in the treatment of neonatal hyperbilirubinemia, but the whole process of ETT needs to be closely monitored.

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

Cited by 18 publications

References 43 publications

Genetic testing of UGT1A1 in the diagnosis of Gilbert syndrome: The discovery of seven novel variants in the Chinese population

Genetic testing of UGT1A1 in the diagnosis of Gilbert syndrome: The discovery of seven novel variants in the Chinese population

Bilirubin metabolism andUDP‐glucuronosyltransferase1A1variants in Asians: Pathogenic implications and therapeutic response

A single-center experience on exchange transfusion therapy in 123 full-term cases of severe neonatal hyperbilirubinemia in Wuhan

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