CONTRIBUTION OF DLG5, MDR1, NOD1/CARD4 AND TLR4 TO PEDIATRIC ONSET INFLAMMATORY BOWEL DISEASE
Bibliographic record
Abstract
Host-bacteria interaction and mucosal barrier function are important in the pathogenesis of inflammatory bowel disease (IBD). Variations in genes that might affect either (MDR1, NOD1/CARD4, TLR4 and DLG5) are suggested to confer susceptibility. We evaluated the contribution of these genes in a single center population of IBD patients diagnosed at age <17 yrs. 358 probands (60% Male) with IBD (251 CD, 107 UC), their parents, and 42 affected siblings were genotyped for MDR1 (rs1045642), NOD1/CARD4 (rs2075820), TLR4 (rs4986790) and DLG5 (1248696, 2289310) polymorphisms. Data were analyzed by transmission disequilibrium testing (TDT) utilizing the family based association test (FBAT). North American IBD Genetics Consortium phenotyping definitions were used. 66% patients were non-Jewish Caucasian and 23% Jewish Caucasian. 24% of CD and 14% of UC probands had affected first degree relative(s). UC was extensive in 77% and 21% had undergone colectomy. CD macroscopically involved small bowel (sb) only (54%); sb and colon (34%); colon only (14%). At most recent follow-up CD was inflammatory (74%) stricturing (9%) and internal penetrating (17%). 30% had undergone intestinal resection. A significant association between MDR1 and CD (P = 0.03) primarily in Jewish patients (P = 0.02) and in sb+colon disease (P = 0.04) was demonstrated. A similar association was seen for TLR4 (CD: P = 0.06; Jewish: P = 0.04; sb+colon: P = 0.02). No association was found between CD and the NOD1/CARD4 or DLG5 polymorphisms, nor between IBD or UC and any of the polymorphisms examined. In this cohort with exclusively early onset IBD, previously described associations between DLG5 and IBD are not replicated. We confirm the association of TLR4 with CD susceptibility. We document a novel association with MDR1. Our findings reinforce the importance of ethnic stratification in genetic studies, and support the role of barrier function and innate immunity in CD pathogenesis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".