Association between polymorphisms of the FOXF1 and MHC locus genes and gastroesophageal reflux disease (GERD).
Bibliographic record
Abstract
15 Background: GERD predisposes to Barrett’s Esophagus (BE), a precursor lesion to esophageal adenocarcinoma (EA). Recently a large genome-wide association study found two germline markers to be associated with BE, FOXF1 rs9936833 (C Allele) and MHC rs9257809 (A allele). An additional study linked FOXF1 rs9936833 to EA. We assessed whether these same polymorphisms are associated with GERD. Methods: Patients with reflux symptoms referred for esophageal manometry/24-hr pH monitoring at University Health Network (Toronto) were enrolled. DNA extracted from blood was genotyped using a Taqman PCR assay. GERD cases were defined as having DeMeester scores of ≥14.7 or prior evidence of reflux esophagitis on endoscopy. DeMeester < 14.7 defined controls. Logistic regression analysis, adjusted for clinical risk factors, was used to calculate odds ratios (95% confidence intervals) for each polymorphism relative to GERD. Results: Of 182 patients, the median age was 50 years, 62% were female and, 52% met the definition for GERD. Males, higher BMI, alcohol consumption, FOXF1, and MHC polymorphisms were each individually associated with GERD. In the multivariate analysis, after adjusting for gender and BMI, FOXF1 rs9936833 remained significant, with an aOR of 1.82 (95%CI: 1.1-3.0; p=0.02) for an increase in each C allele. MHC rs9257809 also remained significant, with an aOR of 9.36 (2.9-30; p<0.001) comparing AA to AG (there were no patients with GG). When both polymorphisms were placed in the same model, the aORs were 2.10 (1.2-3.5; p=0.006) and 11.0 (3.3-36; p<0.001), per increase in each risk allele, respectively. Conclusions: There are strong, significant associations for increased GERD risk by the C allele in FOXF1 rs9936833 and the A allele in MHC rs9257809 among patients complaining of reflux symptoms. FOXF1 is associated with development of gastrointestinal smooth muscle, possibly contributing to the contractibility of the gastroesophageal junction. The MHC polymorphism is in linkage disequilibrium with HLA alleles involved in T-cell regulation, suggesting the possibility of T-cell involvement in reflux esophagitis. WFL and CL are co-first authors. GL and GED are co-senior authors.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".