OV-A-3Genetic determinants of the hepatic expression of the phase II conjugating UGT1A3 enzyme
Bibliographic record
Abstract
BACKGROUND/AIMS UDP-glucuronosyltransferase UGT1A3 is significant for the glucuronic acid conjugation of a diversity of endo- and xenobiotics in the liver. Considering the variability in UGT1A3-mediated hepatic glucuronidation activity, this study was designed to identify common UGT1A3 genetic variants and determine their potential for contributing to interindividual differences. METHODS Single nucleotide polymorphism (SNP) discovery was accomplished by resequencing DNA samples from healthy Caucasians. Haplotypes were inferred and population frequencies estimated using PHASE version 2.1. For functional analysis, we used HepG2 cells in transfection studies with UGT1A3/luciferase constructs and electromobility shift assays. RESULTS Sequence analysis revealed six UGT1A3 upstream SNPs and 4 common (3–26%) promoter region haplotypes were inferred. One of the promoter variants fell within a putative binding factor site for the hepatocyte nuclear factor (HNF)-1α at −148 and is associated with a significant decrease in luciferase activity. The −148 T>C variant significantly decreased by 50% the binding of the protein complex while the HNF1α-specific antibody was able to supershift entirely the DNA-protein complex. CONCLUSION UGT1A3 common promoter haplotype variants modulate gene function, namely through a reduction of the HNF1α-mediated promoter activation, and might contribute to interindividual differences in UGT1A3-mediated glucuronidation. Clinical Pharmacology & Therapeutics (2005) 79, P35–P35; doi: 10.1016/j.clpt.2005.12.124
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".