P763 Fucosyltransferase 2 non-secretor status in Crohn's disease: a prospective observational analysis
Bibliographic record
Abstract
Background: The FUT2 gene encodes fucosyltransferase 2 (FUT2), regulating intestinal antigen secretion and bacterial adherence. FUT2 homozygous mutations (FUT2M) and subsequent non-secretor status is associated with Crohn's disease (CD). A nucleotide polymorphism encoding a nonsense variant may predispose to CD by disrupting bacterial adherence or mucin fucosylation. This alters bacterial and mucous protection against pathogens, causing immune disequilibrium and mucosal inflammation. FUT2 products also interact with the IL 12/23 inflammatory pathways. Supporting genome wide association studies strongly associate homozygous FUT2 SNPs in strong linkage disequilibrium (LD) (rs602662 (A), rs676388 (C), rs492602 (G), rs504963 (A), rs601338 (A), rs485186 (G)), non-secretion, and CD. rs601338 (W143X) is the common null allele in Caucasians associated with the ABO non-secretory phenotype. Methods: We conducted a cross-sectional observational study of consecutive adult CD outpatients at the McGill University Health Center (2013–2015). Clinical and biochemical data were prospectively collected at a single routine office visit. We analyzed associations between CD and FUT2 mutation status. Results: Sixty-two CD patients were recruited. FUT2M homozygotes (rs602662, rs601338 or any mutation in LD) were detected in 27% of CD (17/62). Compared to Wild type (n=18), CD FUT2M homozygotes (n=17) had less penetrating CD (18% vs. 56%, p=0.02) and higher clinical remission without biologic or immunomodulator therapy (47% vs 6%, p=0.006). The latter was not observed in heterozygotes (22%, n=27, p=0.15). CD FUT2M homozygotes had similar disease location in the ileum (L2 p=0.31) and colon (L1, L3, p=0.56). Similarly, patients with homozygous rs601338 (n=15) had increased clinical remission rates without biologic or immunomodulator therapy (53% vs 5%, p=0.0016) compared to patients with wild type status (n=19). This was not observed in heterozygotes (24%, n=25, p=0.09). Both rs601338 homozygotes (20%) and heterozygotes (24%) had less penetrating disease than Wild type (53%, p=0.0495, 0.0478). rs601338 homozygotes (67%) but not heterozygotes (56%) had more luminal phenotype compared to non-mutants (32%, p=0.042). Conclusions: FUT2 homozygous mutations in CD was associated with a milder disease course: lower rates of penetrating disease and higher rates of remission without need for biologic or immunomodulator therapy. FUT2 may play a role in the natural history of CD through mofification of expression of adherence molecules and gut dysbiosis. Further studies are needed to confirm these findings.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".