ArticleHuman molecular genetics2014
Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- A Systematic Review of Parkinson's Disease Pharmacogenomics: Is There Time for Translation into the Clinics?International journal of molecular sciences · 2021Pooled it
- Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population.European journal of clinical pharmacology · 2019Trial
- Polymorphic Expression of UGT1A9 is Associated with Variable Acetaminophen Glucuronidation in Neonates: A Population Pharmacokinetic and Pharmacogenetic Study.Clinical pharmacokinetics · 2018Trial
- Atypical population pharmacokinetics of hydromethylthionine in patients with Alzheimer's disease explains unexpected phase 3 trial results.British journal of clinical pharmacology · 2026Article
- Effect of COMT and UGT1A Variants on Clinical Response to Opicapone in Parkinson's Disease.Movement disorders clinical practice · 2026Article
- The Impact ofGenes · 2026Article
- Safety of COMT-inhibitors in parkinson's disease: a phase-IV comparative study on adverse events of Tolcapone, Entacapone and Opicapone.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Article
- Association of UGT1A1 gene variants, expression levels, and enzyme concentrations with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin.Scientific reports · 2024Article
- The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy.Genes · 2023Review
- The Uridine diphosphate (UDP)-glycosyltransferases (UGTs) superfamily: the role in tumor cell metabolism.Frontiers in oncology · 2022Review
- Concomitant Treatment with Voriconazole and Flucloxacillin: A Combination to Avoid.Antibiotics (Basel, Switzerland) · 2021Article
- An Investigation of the Metabolism and Excretion of KD101 and Its Interindividual Differences: A Microtracing Mass Balance Study in Humans.Clinical and translational science · 2021Article
- The relationship between hyperbilirubinemia and the promoter region and first exon of UGT1A1 gene polymorphisms in Vietnamese newborns.Pediatric research · 2020Article
- Influence of genetic variants and antiepileptic drug co-treatment on lamotrigine plasma concentration in Mexican Mestizo patients with epilepsy.The pharmacogenomics journal · 2020Article
- PharmGKB summary: lamotrigine pathway, pharmacokinetics and pharmacodynamics.Pharmacogenetics and genomics · 2020Review
- Effect of UDP-glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome.The Kaohsiung journal of medical sciences · 2019Article
- Factors Affecting Interindividual Variability of Hepatic UGT2B17 Protein Expression Examined Using a Novel Specific Monoclonal Antibody.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
- Age- and Genotype-Dependent Variability in the Protein Abundance and Activity of Six Major Uridine Diphosphate-Glucuronosyltransferases in Human Liver.Clinical pharmacology and therapeutics · 2019Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV region accounting for variability in UGT2B17 gene transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs.
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