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Genomes and Genes | C GuillemetteSummaryCountry: Canada Publications
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Publications
Regulation of UGT1A1 and HNF1 transcription factor gene expression by DNA methylation in colon cancer cellsAnne Sophie Bélanger
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Quebec, 2705 Laurier, Quebec, G1V 4G2, Canada
BMC Mol Biol 11:9. 2010..Interestingly, one of these CpG dinucleotides (CpG -4) is found close to a HNF1 response element (HRE), known to be involved in activation of UGT1A1 gene expression, and within an upstream stimulating factor (USF) binding site...
Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levelsC Guillemette
Oncology and Molecular Endocrinology Research Center, Laval University Medical Center CHUL, Faculty of Pharmacy, Laval University, Quebec G1V 4G2, Canada
Cancer Epidemiol Biomarkers Prev 10:711-4. 2001..The results presented do not support a strong association between the UGT1A1 promoter polymorphism and the risk of breast cancer...
Pharmacogenomics of human UDP-glucuronosyltransferase enzymesC Guillemette
Oncology and Molecular Endocrinology Research Center, Laval University Medical Center CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada
Pharmacogenomics J 3:136-58. 2003..The pharmacogenomic implication of polymorphic UGTs is presented, more specifically the role of UGT polymorphisms in modifying cancer risk and their impact on individual risk to drug-induced toxicities...
Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 geneC Guillemette
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, USA
Pharmacogenetics 10:629-44. 2000..These findings suggest that further studies are needed to investigate the impact of the low UGT1A7 conjugator genotype on individual susceptibility to chemical-induced diseases and responses to therapeutic drugs...
Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overviewChantal Guillemette
Canada Research Chair in Pharmacogenomics and laboratory of Pharmacogenomics, CHUL Research Center, Quebec, Canada
Breast Cancer Res 6:246-54. 2004..This review addresses the most recent findings on the identification of UGT enzymes that are responsible for the glucuronidation of E2 and its metabolites, and evidence regarding their potential role in breast cancer...
UGT genomic diversity: beyond gene duplicationChantal Guillemette
Pharmacogenomics Laboratory, CHUQ Research Center and Faculty of Pharmacy, Laval University, Quebec City, Quebec, Canada
Drug Metab Rev 42:24-44. 2010..This review will discuss novel molecular aspects that may be determinant to UGT phenotypes...
Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissuesA Belanger
MRC Group in Molecular Endocrinology, CHUL Research Center and Laval University, Quebec, Canada
J Steroid Biochem Mol Biol 65:301-10. 1998..The glucuronidation of steroids by UGT enzymes is an important mechanism by which the levels of steroids is regulated in steroid target tissues...
Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and association with breast cancer among African AmericansC Guillemette
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
Cancer Res 60:950-6. 2000..Our current findings suggest that further investigations are warranted to elucidate the role of UGT1A1 in breast cancer risk...
A pharmacogenomics study of the human estrogen glucuronosyltransferase UGT1A3Bertrand Caillier
Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUQ Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Pharmacogenet Genomics 17:481-95. 2007....
Alternative-splicing forms of the major phase II conjugating UGT1A gene negatively regulate glucuronidation in human carcinoma cell linesJ Bellemare
Pharmacogenomics Laboratory, CHUQ Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Pharmacogenomics J 10:431-41. 2010..This new regulatory strategy may ensure an additional mean to modulate cellular response to endo/xeno stimulus...
The impact of UGT1A8, UGT1A9, and UGT2B7 genetic polymorphisms on the pharmacokinetic profile of mycophenolic acid after a single oral dose in healthy volunteersE Levesque
Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Clin Pharmacol Ther 81:392-400. 2007....
UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liverHugo Girard
Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, 2705 Boulevard Laurier, , Canada
Hepatology 42:448-57. 2005..In conclusion, UGT1A1 polymorphisms modulate the hepatic metabolism of the carcinogenic intermediate of PhIP and may determine the level of its exposure and potentially influence the risk of cancer through dietary exposure to HCAs...
Characterization of common UGT1A8, UGT1A9, and UGT2B7 variants with different capacities to inactivate mutagenic 4-hydroxylated metabolites of estradiol and estroneJean Thibaudeau
Oncology and Molecular Endocrinology Research Center, Faculty of Pharmacy, Laval University, Quebec, Canada
Cancer Res 66:125-33. 2006....
Characterization of UDP-glucuronosyltransferases active on steroid hormonesD W Hum
Laboratory of Molecular Endocrinology, CHUL Research Center, Laval University, Quebec, Canada
J Steroid Biochem Mol Biol 69:413-23. 1999..Steroid conjugation by UGT enzymes is potentially involved in hormone inactivation in steroid target tissues, thus modifications in UGT expression levels may influence hormonal responses...
Expression of transcripts encoding steroid UDP-glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP cell lineG Belanger
MRC Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada
Mol Cell Endocrinol 113:165-73. 1995..Our studies demonstrate the presence of two UGT activities and at least two types of UGT transcripts in both the human prostate and the LNCaP...
The functional UGT1A1 promoter polymorphism decreases endometrial cancer riskYannick Duguay
Canada Research Chair in Pharmacogenomics, Pharmacogenomics Laboratory, Faculty of Pharmacy, Centre Hospitalier de l Université Laval CHUL Research Center, Hotel Dieu de Quebec, Laval University, Quebec, Canada
Cancer Res 64:1202-7. 2004..05)]. These observations suggest that lower expression of UGT1A1 decreases the risk of endometrial cancer by reducing the excretion of 2-hydroxyestradiol, the antiproliferative metabolite of E(2), in the endometrium...
Modulation of the human glucuronosyltransferase UGT1A pathway by splice isoform polypeptides is mediated through protein-protein interactionsJudith Bellemare
Pharmacogenomics Laboratory, Centre Hospitalier de l Université Laval Research Center and Faculty of Pharmacy, Laval University, Quebec G1V 4G2, Canada
J Biol Chem 285:3600-7. 2010..Thus, protein-protein interactions are likely responsible for the inhibition of active UGT1A_i1 by i2 spliced polypeptides. This new regulatory mechanism may alternatively modulate cellular response to endo/xeno stimulus...
Copy-number variations (CNVs) of the human sex steroid metabolizing genes UGT2B17 and UGT2B28 and their associations with a UGT2B15 functional polymorphismVincent Menard
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec CHUQ Research Center, and Pharmacy Department, Laval University, Quebec, Canada
Hum Mutat 30:1310-9. 2009..Restricting the analyses to CNV of the UGT2B17 gene without evaluating UGT2B28 CNV, along with the genotype of UGT2B15, may over- or underestimate the impact of each gene under physiological conditions or disease states...
Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian populationVincent Menard
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Quebec CHUQ Research Center and Laval University, Faculty of Pharmacy, Quebec, Quebec City, Canada
Hum Mutat 30:677-87. 2009..This report provides relevant data for further pharmacogenomic studies...
Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activityHugo Girard
Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Pharmacogenet Genomics 17:1077-89. 2007..Recently, a novel exon (referred to as exon 5b) was identified in the common shared region...
Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new splicing event at the UGT1A locusEric Levesque
Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Hepatology 45:128-38. 2007....
Influence of nonsynonymous polymorphisms of UGT1A8 and UGT2B7 metabolizing enzymes on the formation of phenolic and acyl glucuronides of mycophenolic acidOlivier Bernard
Canada Research Chair in Pharmacogenomics, Pharmacogenomics Laboratory, CHUL Research Center, T3-48, 2705 boul. Laurier, QC, G1V 4G2, Canada
Drug Metab Dispos 34:1539-45. 2006....
Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugsLyne Villeneuve
Pharmacogenomics Laboratory, Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Faculty of Pharmacy, Laval University, Quebec, Canada
J Pharmacol Exp Ther 307:117-28. 2003..Results suggest that these low SN-38 glucuronidating alleles may represent additional molecular determinants of irinotecan-induced toxicity and warrant further investigations...
Identification of common polymorphisms in the promoter of the UGT1A9 gene: evidence that UGT1A9 protein and activity levels are strongly genetically controlled in the liverHugo Girard
Canada Research Chair in Pharmacogenomics, Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Pharmacogenetics 14:501-15. 2004..The great interindividual variability of UGT1A9-mediated glucuronidation remains poorly explained, while evidence for its genetic origin exists...
Cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase is functional in bovine mammary glandV Dostaler-Touchette
Centre de Recherche en Biologie de la Reproduction, Departement des Sciences Animales, Universite Laval, Quebec, Canada
J Dairy Sci 92:3757-65. 2009..93 fmol/min per microg of total protein. In conclusion, these results not only demonstrate the presence of PDE4D transcript and protein, but also show an active enzyme, suggesting a functional role of PDE4D in bovine mammary gland...
Differential regulation of two uridine diphospho-glucuronosyltransferases, UGT2B15 and UGT2B17, in human prostate LNCaP cellsC Guillemette
CHUL Research Center, Laval University, Quebec, Canada
Endocrinology 138:2998-3005. 1997..UGT2B17 was shown to be more labile than UGT2B15, indicating that regulation of UGT2B17 expression would lead to a more rapid change in the level of glucuronidated steroids...
A novel functional polymorphism in the uridine diphosphate-glucuronosyltransferase 2B7 promoter with significant impact on promoter activityYannick Duguay
Canada Research Chair in Pharmacogenomics, Laboratory of Pharmacogenomics, CHUL Research Center, 2705 Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2
Clin Pharmacol Ther 75:223-33. 2004..96) and 31.2 +/- 17.1 versus 42.9 +/- 31.2 for M3G/morphine (P =.53), respectively. Further studies in larger samples are needed to make conclusions about the possible clinical relevance of the -79 polymorphism in the UGT2B7 gene...
Deferiprone glucuronidation by human tissues and recombinant UDP glucuronosyltransferase 1A6: an in vitro investigation of genetic and splice variantsMarie Odile Benoit-Biancamano
CHUQ Research Center, 2705, Boul Laurier, T3 48, G1V 4G2, Quebec, QC, Canada
Drug Metab Dispos 37:322-9. 2009..Genetic variations and differences in the expression of splice variants represent a potential source of variation in deferiprone metabolism...
Pharmacokinetics of mycophenolate mofetil and its glucuronide metabolites in healthy volunteersEric Levesque
Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, T3 48, 2705 Boul Laurier, Quebec, G1V 4G2, Canada
Pharmacogenomics 9:869-79. 2008..We previously reported that polymorphisms in the UGT2B7 and UGT1A9 genes are associated with significant alteration in the disposition of mycophenolic acid (MPA) in healthy volunteers...
Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38)Jean François Gagné
Faculty of Pharmacy, Laval University, Quebec, Canada
Mol Pharmacol 62:608-17. 2002..Taken together, these data provide the evidence that molecular determinants of irinotecan response may include the UGT1A polymorphisms studied herein and common genetic variants of the hepatic UGT1A9 isoenzyme yet to be described...
Glucuronidation of the antiretroviral drug efavirenz by UGT2B7 and an in vitro investigation of drug-drug interaction with zidovudineAnne Sophie Bélanger
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada
Drug Metab Dispos 37:1793-6. 2009..We conclude that UGT2B7 has a major role in EFV glucuronidation and that EFV could potentially interfere with the hepatic glucuronidation of AZT...
The human UGT1A3 enzyme conjugates norursodeoxycholic acid into a C23-ester glucuronide in the liverJocelyn Trottier
Laboratory of Molecular Pharmacology, CHUQ Research Center, and the Faculty of Pharmacy, Laval University, Quebec, Quebec G1V 4G2, Canada
J Biol Chem 285:1113-21. 2010....
Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in colon cancerJean Francois Gagnon
Canada Research Chair in Pharmacogenomics, Centre Hospitalier de l Universite Laval Research Center, Faculty of Pharmacy, Laval University, Quebec, Canada
Clin Cancer Res 12:1850-8. 2006..Herein, we explored the role of DNA methylation in the silencing of UGT1A1 gene expression in colon cancer and its influence on cellular SN-38 detoxification...
Extensive splicing of transcripts encoding the bile acid-conjugating enzyme UGT2B4 modulates glucuronidationEric Levesque
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Quebec CHUQ, Canada
Pharmacogenet Genomics 20:195-210. 2010..UGT2B4 is involved in bile acids metabolism and highly expressed in liver and extrahepatic tissues. The aim of this study was to uncover new molecular mechanisms underlying interindividual variability in the UGT2B4 pathway...
Circulating estrogens in endometrial cancer cases and their relationship with tissular expression of key estrogen biosynthesis and metabolic pathwaysJohanie Lepine
Centre Hospitalier Universitaire de Québec Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada G1V 4G2
J Clin Endocrinol Metab 95:2689-98. 2010....
Profiling of endogenous estrogens, their precursors, and metabolites in endometrial cancer patients: association with risk and relationship to clinical characteristicsEtienne Audet-Walsh
Centre Hospitalier Universitaire de Quebec Research Center, Laval Universiy, Quebec, Canada
J Clin Endocrinol Metab 96:E330-9. 2011..Endometrial cancer (EC) predominantly occurs after menopause and is strongly related to steroid hormones, particularly estrogens. However, the relationship between these hormones and clinical characteristics remains unaddressed...
In vitro investigation of human UDP-glucuronosyltransferase isoforms responsible for tacrolimus glucuronidation: predominant contribution of UGT1A4Isabelle Laverdière
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de Quebec Research Center, Quebec, Canada
Drug Metab Dispos 39:1127-30. 2011..We conclude that UGT1A4 is the major isoform involved in Tacro glucuronidation, whereas additional studies are required to assess the contribution of UGT1A4 genetic factors in tacrolimus glucuronidation variability...
In vitro glucuronidation of fenofibric acid by human UDP-glucuronosyltransferases and liver microsomesJelena Tojcic
Pharmacogenomics Laboratory, Centre Hospitalier Universitaire de L Université Laval Research Center and Faculty of Pharmacy, Laval University, Quebec, Quebec, Canada
Drug Metab Dispos 37:2236-43. 2009..Additional studies are required to identify genetic factors contributing to the observed FA glucuronidation variability...
Profiling endogenous serum estrogen and estrogen-glucuronides by liquid chromatography-tandem mass spectrometryPatrick Caron
Centre Hospitalier Universitaire du Quebec Research Center, Laval University, Quebec, Canada G1V 4G2
Anal Chem 81:10143-8. 2009..In serum of postmenopausal women, E(1)-3G was the most abundant estrogen found (30.9 pg/mL). Our method profiles estrogens and estrogen-glucuronides and may represent a new tool to identify biomarkers in hormone-dependent diseases...
The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variantsOlivier Bernard
Canada Research Chair in Pharmacogenomics, Pharmacogenomics Laboratory, CHUL Research Center, T3 48, 2705 Boulevard Laurier, Quebec, G1V 4G2, Canada
Drug Metab Dispos 32:775-8. 2004..Our study provides preliminary evidences that genetic factors, especially in the hepatic UGT1A9, may contribute to the variability of MPA pharmacokinetics observed in transplant patients...
UGT1A1 and UGT1A9 functional variants, meat intake, and colon cancer, among Caucasians and African-AmericansHugo Girard
Pharmacogenomics Laboratory, CHUQ Research Center and Faculty of Pharmacy, Laval University, G1V 4G2 Quebec, Canada
Mutat Res 644:56-63. 2008..7 ng/day and combined high/intermediate genotypes. These data support a hypothesis that UGTs modify the association between meat-derived PAH exposure and colon cancer by their role in the elimination of dietary carcinogens...
Joint effects between UDP-glucuronosyltransferase 1A7 genotype and dietary carcinogen exposure on risk of colon cancerLesley M Butler
Department of Public Health Sciences, Division of Epidemiology, University of California, Davis, California, USA
Cancer Epidemiol Biomarkers Prev 14:1626-32. 2005..2-4.8), compared with less than the median daily intake and UGT1A7 high/intermediate genotypes. These data suggest that the associations among cooked meat-derived compound exposure, and colon cancer are modified by the UGT1A7 genotype...
Polymorphisms in steroid hormone pathway genes and mammographic densityChristopher A Haiman
Department of Epidemiology, Harvard School of Public Health Boston, MA, USA
Breast Cancer Res Treat 77:27-36. 2003..However, our findings of differences in associations for UGT1A1 and AIB1 genotypes with breast density by menopausal status needs additional corroboration...
The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liverHugo Girard
Laboratory of Pharmacogenomics, , Quebec, QC, Canada G1V 4G2
Drug Metab Dispos 34:1220-8. 2006....
Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometriumJohanie Lepine
Department of Molecular Endocrinology and Oncology, G1V 4G2 Quebec, Canada
J Clin Endocrinol Metab 89:5222-32. 2004..Data show that several UGT enzymes detected in the endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2-MeO metabolites that exert various biological effects in the tissue...
In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymesJacqueline Ramirez
Department of Medicine, University of Chicago, Illinois 60637, USA
Pharm Res 19:588-94. 2002....
Characterization of benzo(a)pyrene-trans-7,8-dihydrodiol glucuronidation by human tissue microsomes and overexpressed UDP-glucuronosyltransferase enzymesJia-Long Fang
Divisions of Cancer Control and Molecular Oncology, H. Lee Moffitt Cancer Center, Interdisciplinary Oncology Program and Departments of Biochemistry and Pharmacology and Therapeutics, University of South Florida, Tampa, Florida 33612, USA
Cancer Res 62:1978-86. 2002....
Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9Michael H Court
Comparative and Molecular Pharmacogenetics Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
Drug Metab Dispos 30:1257-65. 2002..Allelic variation associated with the UGT2B15 gene may explain polymorphic S-oxazepam glucuronidation in humans...
Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamilyPeter I Mackenzie
Department of Clinical Pharmacology, Flinders University School of Medicine, Flinders Medical Center, Bedford Park, Australia
Pharmacogenet Genomics 15:677-85. 2005..Most UGT1 and UGT8 enzymes have been characterized in detail; however, the catalytic functions of the UGT3A enzymes and several UGT2 enzymes remain to be characterized...
Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor 4alphaOlivier Barbier
Unité INSERM 545, Institut Pasteur de Lille, 1 rue du Pr Calmette, BP 245, 59019 Lille, France
Mol Pharmacol 67:241-9. 2005....
The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target geneOlivier Barbier
UR 545 INSERM, Departement d Atherosclerose, Institut Pasteur de Lille and the Faculté de Pharmacie, Universite de Lille II, France
J Biol Chem 278:13975-83. 2003..Furthermore, since UGT1A9 is involved in the catabolism of fibrates, these results suggest that PPAR alpha and PPAR gamma may control the intracellular level of active fibrates...
Glucuronidation and the UDP-glucuronosyltransferases in health and diseasePeter G Wells
Faculty of Pharmacy and Department of Pharmacology, University of Toronto, Ontario, Canada
Drug Metab Dispos 32:281-90. 2004....
