NADPH oxidase complex and IBD Candidate Gene studies
Bibliographic record
Abstract
The NOX2 NADPH oxidase complex produces reactive oxygen species and plays a critical role in microbe killing by phagocytes. Genetic mutations in genes encoding components of the complex result in both X-linked and autosomal recessive forms of Chronic Granulomatous Disease (CGD). CGD patients often develop intestinal inflammation that is histologically similar to Crohn's colitis, suggesting a common etiology for both diseases. The aim of this study is to determine if polymorphisms in NOX2 NADPH oxidase complex genes that do not cause CGD are associated with the development of Inflammatory Bowel Disease (IBD). Direct sequencing and candidate gene approaches were used to identify susceptibility loci in NADPH oxidase complex genes. Functional studies were carried out on identified variants. Novel findings were replicated in independent cohorts. Sequence analysis identified a novel missense variant in the NCF2 gene (neutrophil cytosolic factor 2) that is associated with very early-onset IBD (VEO-IBD) and subsequently found in 4% of VEO-IBD patients versus 0.2% of controls (P = 1.3 × 10-5, OR = 23.8 (3.9 - 142.5); Fischer Exact Test). This variant reduced binding of the NCF2 gene product p67phox to RAC2. We report a novel genetic association with RAC2 and CD and replicate the previously reported association of NCF4 with ileal CD. These studies suggest that the rare novel p67phox variant results in partial inhibition of oxidase function and is associated with CD in a subgroup of patients with VEO-IBD; and suggest that components of the NADPH oxidase complex are associated with CD. Accepted in Gut.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".