Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease
Bibliographic record
Abstract
Abstract Background E-cadherin, a major actor of cell adhesion in the intestinal barrier, is encoded by the CDH1 gene and associated with susceptibility to Crohn's Disease (CD) and colorectal cancer. Since epigenetic mechanisms are suspected to contribute to the pathogenesis of CD, we studied the methylation of the CpG island (CGI) located in the CDH1 promoter and of 4 CpGs in the 7th enhancer in inflamed ileal mucosa and PBMC of CD patients operated on. Patients who underwent surgery for a non-inflammatory bowel disease provided a macroscopically normal ileal mucosa and PBMC for comparison. Results In ileal mucosa, 90% of the 21 studied CD patients had a methylated CDH1 CGI vs 50% of the 16 control patients (P < 0.01). In PBMC, percentage was comparable in CD (52%) and controls (44%). The methylation of the 4 CpGs in the 7th enhancer of CDH1 was also higher in the CD group for each individual CpG and for the average of the 4 CpGs (45 ± 17% in CD patients vs 36 ± 17% in controls, P < 0.001), while it was comparable in PBMC. The rs16260 SNP known to be associated with CD was not associated with studied CpG methylation. Conclusion Independently of the rs16260 genotype, the methylation of the promoter CGI and 4 enhancer CpGs at the CDH1 locus was increased in the inflamed ileal mucosa of a small cohort of CD patients. We speculate that these local methylation changes may decrease local expression of E-cadherin (not studied) and favor or aggravate ileal CD lesions. Whether CGI methylation could be used as a biomarker of colorectal cancer risk in ileal biopsies will have to be explored in further studies.
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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 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".