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UDP glucuronosyltransferase 1 family, polypeptide A1

UGT1A1, UGT1A, UGT1, bilirubin UDP-glucuronosyltransferase
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008] (from NCBI)
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Top mentioned proteins: Glucuronosyltransferase, UDP-glucuronosyltransferase, UGT, CAN, HAD
Papers on UGT1A1
Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians.
New
Kawai et al., Tokyo, Japan. In Br J Clin Pharmacol, Feb 2016
Intrinsic factors (polymorphism of UGT1A1 for moxifloxacin, SLCO1B1 for simvastatin, and CYP2C9 for meloxicam) were also examined.
Efflux Transport Characterization of Resveratrol Glucuronides in UDP-Glucuronosyltransferase 1A1 Transfected Hela Cells: Application of a Cellular Pharmacokinetic Model to Decipher the Contribution of Multidrug Resistance-Associated Protein 4.
New
Wu et al., Jinan, China. In Drug Metab Dispos, Feb 2016
Here we aimed to characterize the efflux transport of resveratrol glucuronides using UGT1A1-overexpressing HeLa cells (HeLa1A1 cells), and to determine the contribution of multidrug resistance-associated protein 4 (MRP4) to cellular excretion of the glucuronides.
Three-dimensional polyacrylamide gel-based DNA microarray method effectively identifies UDP-glucuronosyltransferase 1A1 gene polymorphisms for the correct diagnosis of Gilbert's syndrome.
New
Wu et al., Nanjing, China. In Int J Mol Med, Feb 2016
UNASSIGNED: Gilbert's syndrome is a mild genetic liver disorder characterized by unconjugated hyperbilirubinemia due to defects in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene.
UGT genotyping in belinostat dosing.
Review
New
Figg et al., Bethesda, United States. In Pharmacol Res, Feb 2016
UNASSIGNED: Certain genetic polymorphisms of UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) can reduce gene expression (*28, *60, *93) or activity (*6), thereby altering the pharmacokinetics, pharmacodynamics, and the risk of toxicities of UGT1A1 substrates, of which irinotecan is a widely-described example.
High Resectability Rate of Initially Unresectable Colorectal Liver Metastases After UGT1A1-Adapted High-Dose Irinotecan Combined with LV5FU2 and Cetuximab: A Multicenter Phase II Study (ERBIFORT).
New
Rivoire et al., Saint-Étienne, France. In Ann Surg Oncol, Feb 2016
BACKGROUND: The purpose of this study was to assess the efficacy and tolerance of induction chemotherapy combining LV5FU2 with increased doses of irinotecan adapted to UGT1A1 genotyping and cetuximab in untreated potentially resectable liver metastases of colorectal cancer.
Association between UGT1A1 Polymorphism and Risk of Laryngeal Squamous Cell Carcinoma.
New
Li et al., Taiyuan, China. In Int J Environ Res Public Health, Dec 2015
In conclusion, the rs4148323 G allele is associated with the high UGT1A1 enzyme activity, and might increase the risk of laryngeal cancer.
Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.
Review
New
Tukey et al., Tokyo, Japan. In Toxicol Appl Pharmacol, Dec 2015
Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing.
Review
New
Haas et al., Pullman, United States. In Clin Pharmacol Ther, Oct 2015
Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37).
[UGT1A1 Genotyping for Proper Use of Irinotecan].
Review
New
Ando et al., In Rinsho Byori, Jul 2015
Recent pharmacogenetic studies on irinotecan have revealed the impact of UGT1A1 polymorphisms on severe adverse effects.
[Companion Diagnostics Sub-Section of Anatomic Pathology Department in a Mid-Sized General Hospital: Start Up and Maintenance].
Review
New
Yasuhara et al., In Rinsho Byori, Jul 2015
Analyses of KRAS and EGFR gene mutations and UGT1A1 polymorphisms should be performed within an anatomic pathology department, in order to obtain results of genetic analysis and start tailor-made pharmacotherapy as soon as possible.
Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer.
Impact
Ratain et al., Evanston, United States. In J Clin Oncol, 2014
PURPOSE: The risk of severe neutropenia from treatment with irinotecan is related in part to UGT1A1*28, a variant that reduces the elimination of SN-38, the active metabolite of irinotecan.
The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation.
Impact
Borden et al., Montréal, Canada. In Nature, 2014
We observe that the sonic hedgehog transcription factor glioma-associated protein 1 (GLI1) and the UDP glucuronosyltransferase (UGT1A) family of enzymes are elevated in resistant cells.
Gilbert syndrome: the UGT1A1*28 promoter polymorphism as a biomarker of multifactorial diseases and drug metabolism.
Review
GeneRIF
Sąsiadek et al., Wrocław, Poland. In Biomark Med, 2012
The UGT1A1*28/*28 genotype has emerged as an important element in drug tolerance, as well as in multifactorial diseases, such as cancer. [Review]
[Genetic factors in the occurrence of neonatal unconjugated hyperbilirubinemia].
GeneRIF
Liu et al., Shenzhen, China. In Zhongguo Dang Dai Er Ke Za Zhi, 2012
UGT1A1 Gly71Arg and G6PD gene mutations may be involved in the development of neonatal unconjugated hyperbilirubinemia.
Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancer.
GeneRIF
Dimovski et al., Скопје, Macedonia. In Cancer Genet, 2012
results indicate that the UGT1A1*28 allele is a risk factor for colorectal cancer in the Macedonian male population, whereas no significant risk was detected among women
Non tumoral hyperserotoninaemia responsive to octreotide due to dual polymorphism in UGT1A1 and UGT1A6.
GeneRIF
Yovos et al., Thessaloníki, Greece. In Hormones (athens), 2012
Dual polymorphisms of UDP glucuronosyl-transferases 1A6 and 1A1 in a patient with Gilbert's syndrome who had persistent hyperserotoninemia that responded to octreotide are reported.
Wayward effect of polymorphism (TA)8 in the promoter region of UGT1A1 gene in a Mexican family.
GeneRIF
Figuera et al., Guadalajara, Mexico. In West Indian Med J, 2012
report of the varied effects of Gilbert syndrome (GS) in a Mexican Mestizo family with a non-common (TA)8 repeat in the promoter region of UGT1A1; report supports that the (TA)7 and (TA)8 are necessary, but not enough to explain the features of GS
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
Impact
Chanock et al., Bethesda, United States. In Nat Genet, 2010
rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1.
Germline genetic variation, cancer outcome, and pharmacogenetics.
Review
Impact
Liu et al., Toronto, Canada. In J Clin Oncol, 2010
Putative germline pharmacogenetic predictors of outcome include DPYD polymorphisms and fluorouracil toxicity, UGT1A1 variation and irinotecan toxicity, and CYP2D6 polymorphisms and tamoxifen efficacy, with emerging data on predictors of molecularly targeted or biologic drugs.
Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05.
Impact
Laurent-Puig et al., Villejuif, France. In J Clin Oncol, 2010
Twenty polymorphisms within the DPD, TS, MTHFR, ERCC1, ERCC2, GSTP1, GSTM1, GSTT1, and UGT1A1 genes were genotyped.
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