Abstract 68: The WWOX Gene Modulates HDL Metabolism and Lipoprotein Gene Expression
Bibliographic record
Abstract
Low plasma HDL cholesterol (HDL-C) constitutes a major risk factor for coronary artery disease. We previously identified a region-wide association between low HDL-C and the WW domain-containing oxidoreductase ( WWOX ) gene in dyslipidemic families and low HDL-C cases and controls (rs2548861, P=6.9x10 -7 ). Here, through a combination of in vivo functional studies, gene microarray and next generation resequencing, we investigated the role of WWOX in lipoprotein and HDL metabolism. Using total Wwox -/- and Wwox liver-specific ( hep -/- ) mice, we found decreased apoA-I and ABCA1 protein levels in hepatic tissues. Analyses of lipoprotein profiles in Wwox -/- littermates also showed marked reductions in serum HDL-C and apoA-I levels, with no effect in Wwox hep -/- mice. A sex-specific difference was however observed in female Wwox hep -/- mice, showing a significant increase in plasma triglycerides levels. We further obtained evidence of a gender-specific effect by gene microarray analyses in Wwox hep -/- hepatocytes, where it was identified that WWOX disruption alters primarily lipid metabolic pathways in females. We observed a significant reduction (P<0.05,
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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) | 0.001 | 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 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".