Evaluation of HIVEP3 polymorphic variants and gene expression in Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background It has been increasingly recognized that neuroinflammation plays an important role in the pathophysiology of Alzheimer’s disease (AD). The HIVEP3 gene encodes a transcription factor that regulates inflammatory response, and variants in this gene have been associated with increased risk for Parkinson’s disease. HIVEP3 gene expression is transiently decreased following nerve damage, consistent with a role during neuronal remodeling . In the present work, we investigate genetic variants in the HIVEP3 gene as risk factors for AD, and study HIVEP3 gene expression in human cerebral cortex. Method We have used three different cohorts to assess the association of HIVEP3 polymorphisms with the risk of developing AD: the International Genomics of Alzheimer’s Project (IGAP), the Quebec Founder Population Cohort (QFP) and Kunkle et al. stage 1 GWAS dataset. In the QFP cohort, we measured HIVEP3 protein levels (using ELISA) and mRNA levels (using RT‐PCR) in the frontal cortex of autopsied‐confirmed AD and control subjects. Result We have found that the rs10493098 C variant is associated with increased risk of AD in IGAP 2009 (p = 0.018, OR = 1.04), QFP (p< 5 × 10−8, OR = 1.37) and Kunkle et al. 2019 stage 1 IGAP GWAS (p = 0.006). In the IGAP cohort, this variant is associated with increased risk of AD only in APOE4 negative participants (p = 0.0009). Cortical HIVEP3 protein levels are increased in subjects with AD compared to controls (p = 0.029) and in subjects with at least one copy of the rs10493098 C variant compared to non‐carriers (p = 0.03). There are no changes in mRNA levels as a function of disease status or presence of the rs10493098 C variant. There is no correlation between HIVEP3 protein or mRNA levels and senile plaques or neurofibrillary tangles densities. Conclusion We have identified a new genetic variant associated with increased risk for AD. The HIVEP3 rs10493098 C variant is associated with increased risk of AD, particularly in APOE4 negative participants. HIVEP3 proteins levels are increased in the frontal cortex of AD subjects compared to controls and in rs10493098 C carriers.
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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 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".