A170 DISTRIBUTION OF PHARMACOGENETIC VARIANTS IN PEOPLE SUFFERING FROM ULCERATIVE COLITIS TREATED WITH TARGETED MOLECULAR THERAPIES IN QUEBEC
Bibliographic record
Abstract
Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous colonic inflammation. In Canada, ~160,000 people suffer from its symptoms, such as diarrhea, blood in the stool and abdominal pain, which can highly impact their quality of life. For moderate to severe forms of the disease, molecular targeted therapies (MTT) are used to control symptoms and achieve remission. There is a large variability in treatment response to MTT. Indeed, ~20-50% MTT users don’t improve following drug initiation and 50-90% suffer from adverse events. Multiple factors, such as age, sex, tobacco use and pharmacogenetic (PGx) variants, may influence response. However, genetic variants may also impact UC development which may become a confounding factor in treatment response studies. Aims Therefore, the aim of this study is to validate PGx variants associated with nonresponse by comparing their distribution in UC patients with a populational cohort. Methods A cohort of 101 people using MTT in UC in Saguenay–Lac-St-Jean was recruited and compared to the populational cohort of CARTaGENE (representing Quebec population, n = 1879). The patients were genotyped for eight PGx variants, distributed across four genes (TNF, TNFAIP3, TNFRSF1A et TNFRSF1B), which were selected as candidates for their previous association with MTT response phenotypes. Results The variant TNFRSF1B-rs1061622, previously associated with nonresponse to infliximab (a type of MTT) in a previous study by our team, was comparable between the recruited and populational cohorts. The alternative allele of variant TNFRSF1B-rs3397 was more frequent in the recruited cohort compared to the populational cohort (80,0 vs 67,0 %, p = 0.0001). No other tested variants were differently distributed. Conclusions Next steps are to compare these PGx variants with a populational cohort of healthy individuals (exclude individuals suffering from UC in CARTaGENE cohort) to eliminate as many confounding factors as possible. The variant TNFRSF1B-rs1061622 would then be validated and become a great lead to better comprehend treatment response to infliximab in UC. The variant TNFRSF1B-rs3397 needs to be studied more to clarify its potential link to UC development. Funding Agencies CCCFRQS, IRSC, Fondation de ma vie
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
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".