Variations in the UDP-Glucuronosyltransferase 1A1 Gene for the Development of Unconjugated Hyperbilirubinemia in Taiwanese

Huang, Yeen; Huang, May-Jen; Yang, Sieng-Sien; Teng, Hsiu-Chen; Huang, Ching‐Shan

doi:10.2217/14622416.9.9.1229

Cited by 15 publications

(37 citation statements)

References 26 publications

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“…The allele frequency of c.-3279T>G is as high as 0.39 in the general Caucasian population [12], which is similar to that in the Taiwanese population (0.37) [5]. However, such a mutation is often ignored when the UGT1A1 gene is analyzed [5]. Mimura et al [13] analyzed whether the polymorphism c.1091C>T in UGT1 isoforms affects glucuronidation of various drugs and found that the polymorphism in UGT1A resulted in lower activities towards β-estradiol, acetaminophen, propofol, lamotrigine, imipramine and cyproheptadine than the wild-type.…”

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

“…DNA sequencing methods were performed to determine the nucleotides at position -3279, those in the promoter area and those in the five exons of the UGT1A1 gene as described previously [5,6]. The nucleotides at positions 388 and 521 in the OATP2 gene were determined by PCR-restriction fragment length polymorphism analysis as described previously [7].…”

Section: Case Reportmentioning

confidence: 99%

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Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the UDP-glucuronosyltransferase 1A1 Gene

Tsai²,

Shih³

et al. 2016

Neonatology

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The total bilirubin value of a male infant was 385 μmol/l on day 5. Liver function test results were normal and there was no evidence of sepsis and no hemolysis reaction. Phototherapy was administered and on day 8 the patient's total bilirubin level was 255 μmol/l. Intermittent episodes of hyperbilirubinemia occurred without phototherapy, with the total bilirubin level reaching 335 μmol/l on day 19. A 3-day regimen of phenobarbital was administered and on day 24 his total bilirubin level was 180 μmol/l. The patient was discharged. At the age of 2 months, the total bilirubin value was 27 μmol/l. His direct bilirubin value was <15% of total bilirubin in every determination. A family study of the UDP-glucuronosyltransferase(UGT)1A1 gene showed that the infant carries a homozygous mutation at nucleotide -3279 plus compound heterozygous mutations at nucleotides 782 and 1091. The mutation at nucleotide 782 is a novel finding. Gilbert's syndrome was diagnosed.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

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Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the UDP-glucuronosyltransferase 1A1 Gene

Tsai²,

Shih³

et al. 2016

Neonatology

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“…In particular, the *28 [(TA) 7 TAA] allele accounts for most of the UGT1A1 polymorphisms seen in the literature, and the level of UGT1A1 activity has been the focus of most studies. 7,8 On the other hand, among Asians, the *6 [211G > A] and *27 [686C > A] alleles are more commonly found in comparison with white populations, and the *37 [(TA) 8 TAA] allele is less common except for African populations. 8 In this study, we aimed to clarify the contribution of UGT1A1 polymorphisms to plasma raltegravir concentrations in Asian patients.…”

Section: Introductionmentioning

confidence: 99%

Short Communication: Lack of Correlation Between *UGT1A1**6, *28 Genotypes, and Plasma Raltegravir Concentrations in Japanese HIV Type 1-Infected Patients

Hirano

Ikemura

Takahashi

et al. 2012

AIDS Research and Human Retroviruses

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Raltegravir is metabolized by glucuronidation via UDP-glucuronosyltransferase 1A1 (UGT1A1). We analyzed the genotypes of UGT1A1 (*6, *27, and *28) and their contribution to plasma raltegravir concentrations in 56 Japanese HIV-1-infected patients in the National Hospital Organization Nagoya Medical Center of Japan. Among the 56 patients, the UGT1A1 genotype in two patients was *6 homozygote. Heterozygous variants were found in 13 patients for *6 and in 11 patients for *28, while all of the patients were found to carry wild-type sequences at the position corresponding to the *27 allele. Plasma raltegravir concentration of a male patient with *6 homozygote (0.53 μg/ml) was modestly higher than that of patients with wild type (0.12 μg/ml) or *6 heterozygote (0.16 μg/ml). Another female patient with the *6 homozygote had a low plasma raltegravir concentration (0.03 μg/ml). Patients heterozygous for the *6 or *28 allele did not display significantly different plasma raltegravir concentrations compared to patients homozygous for the respective wild-type allele. Thus, in the present study, we showed that heterozygous reduced-function *6 and *28 alleles appear to have no significant effect on plasma raltegravir concentrations in Japanese HIV-1-infected patients. However, variability in raltegravir concentration and small patient population precluded a correlation between UGT1A1*6 homozygosity and plasma raltegravir concentration. To clarify the contribution of UGT1A1*6 or *28 polymorphisms to plasma raltegravir concentrations, further investigations on larger subject populations are required.

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“…These data suggest that in addition to the TA7 allele, the Ϫ3279G allele has an effect to further lower the UGT1A1 transcription level. The Ϫ3279G allele has been suggested to associate with poor metabolism of bilirubin by UGT1A1 in hyperbilirubinemia and Gilbert's syndrome (Sugatani et al, 2002;Maruo et al, 2004;Huang et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms in the TATA Box and Upstream Phenobarbital-Responsive Enhancer Module of the UGT1A1 Promoter Have Combined Effects on UDP-Glucuronosyltransferase 1A1 Transcription Mediated by Constitutive Androstane Receptor, Pregnane X Receptor, or Glucocorticoid Receptor in Human Liver

Li¹,

Buckley²,

Wang³

et al. 2009

Drug Metab Dispos

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ABSTRACT:Transcription of UDP-glucuronosyltransferase (UGT) 1A1 is regulated by the transcription factors, constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucocorticoid receptor (GR), hepatocyte nuclear factor (HNF) 1␣, and HNF4␣. The purpose of this study was to determine whether the genetic polymorphisms in the RNA polymerase II core promoter and the upstream phenobarbital-responsive element module (PBREM) of the UGT1A1 promoter have combined effects on UGT1A1 transcription mediated by the transcription factors. A polymorphism of A(TA) 5-8 TAA in the UGT1A1 TATA box and a single nucleotide polymorphism of ؊3279T>G in PBREM were genotyped in 98 human liver samples. Relative mRNA levels of CAR, PXR, GR, HNF1␣, HNF4␣, and UGT1A1 were quantified by a multiplex branched DNA technique. Correlations of mRNA levels between UGT1A1 and the transcription factors were established in liver samples with different combined genetic polymorphisms. Correlation of mRNA levels between UGT1A1 and CAR, PXR, or GR, but not HNF1␣ or HNF4␣, was abolished in the samples with the combined genotype of TA7/7 plus ؊3279G/G, which was also associated with significantly lower UGT1A1 mRNA levels compared with other combined genotypes. Correlations of mRNA levels between UGT1A1 and CAR or PXR were reduced but not abolished in the samples with the combined genotype of TA6/7 plus ؊3279 G/G, which showed significantly lower UGT1A1 mRNA levels compared with the combined genotype of TA6/7 plus ؊3279T/G and other genotypes containing TA6/6. In conclusion, the combined genotypes containing A(TA) 7 TAA and ؊3279G decrease UGT1A transcription mediated by CAR, PXR, or GR but not by HNF1␣ or HNF4␣.

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Variations in the UDP-Glucuronosyltransferase 1A1 Gene for the Development of Unconjugated Hyperbilirubinemia in Taiwanese

Abstract: The c.-3279T>G variant is a further factor for the development of hyperbilirubinemia. Our results also demonstrate that possessing the 60/60 plus 28/28 diplotype in the UGT1A1 gene is a determinant of relatively higher bilirubin values amongst hyperbilirubinemic patients.

Cited by 15 publications

References 26 publications

Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the <b><i>UDP-glucuronosyltransferase 1A1</i></b> Gene

Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the <b><i>UDP-glucuronosyltransferase 1A1</i></b> Gene

Short Communication: Lack of Correlation Between *UGT1A1**6, *28 Genotypes, and Plasma Raltegravir Concentrations in Japanese HIV Type 1-Infected Patients

Genetic Polymorphisms in the TATA Box and Upstream Phenobarbital-Responsive Enhancer Module of the UGT1A1 Promoter Have Combined Effects on UDP-Glucuronosyltransferase 1A1 Transcription Mediated by Constitutive Androstane Receptor, Pregnane X Receptor, or Glucocorticoid Receptor in Human Liver

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Variations in the UDP-Glucuronosyltransferase 1A1 Gene for the Development of Unconjugated Hyperbilirubinemia in Taiwanese

Abstract: The c.-3279T>G variant is a further factor for the development of hyperbilirubinemia. Our results also demonstrate that possessing the *60/*60 plus *28/*28 diplotype in the UGT1A1 gene is a determinant of relatively higher bilirubin values amongst hyperbilirubinemic patients.

Cited by 15 publications

References 26 publications

Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the <b><i>UDP-glucuronosyltransferase 1A1</i></b> Gene

Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the <b><i>UDP-glucuronosyltransferase 1A1</i></b> Gene

Short Communication: Lack of Correlation Between UGT1A1*6, *28 Genotypes, and Plasma Raltegravir Concentrations in Japanese HIV Type 1-Infected Patients

Genetic Polymorphisms in the TATA Box and Upstream Phenobarbital-Responsive Enhancer Module of the UGT1A1 Promoter Have Combined Effects on UDP-Glucuronosyltransferase 1A1 Transcription Mediated by Constitutive Androstane Receptor, Pregnane X Receptor, or Glucocorticoid Receptor in Human Liver

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Resources

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Abstract: The c.-3279T>G variant is a further factor for the development of hyperbilirubinemia. Our results also demonstrate that possessing the 60/60 plus 28/28 diplotype in the UGT1A1 gene is a determinant of relatively higher bilirubin values amongst hyperbilirubinemic patients.

Short Communication: Lack of Correlation Between *UGT1A1**6, *28 Genotypes, and Plasma Raltegravir Concentrations in Japanese HIV Type 1-Infected Patients