Role of the «proprotein convertase subtilisin/kexin 5» gene in high-density lipoprotein metabolism: potential implications for atherosclerotic cardiovascular disease development
Why this work is in the frame
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Bibliographic record
Abstract
Low plasma high-density lipoprotein cholesterol (HDL-C) is a wellestablished risk factor for coronary artery disease (CAD).The proprotein convertase subtilisin/kexin 5 (PC5/PCSK5) is known to inactivate endothelial lipase, enzyme critical in modulating HDL-C levels.In this study, we investigated the role of human PCSK5 genetic variants on HDL-C.We examined haplotypes at the PCSK5 locus in 9 multigenerational families with HDL-C<10 th percentile and discovered segregation with low HDL-C in one family.We genotyped novel single nucleotide polymorphisms (SNPs) found through sequencing and tagSNPs from the HapMap Project (n=182 total) in 457 individuals with CAD and identified 9 SNPs associated with HDL-C (P<0.05), the strongest being rs11144782 (minor allele frequency 0.164, p=0.002).This SNP decreased HDL-C by 0.076 mmol/L in a gene dosage-effect and was also associated with very lowdensity lipoprotein (P=0.039),triglycerides (P=0.049) and apolipoprotein B (P=0.022) levels.We conclude that variability at PCSK5 influences HDL-C levels and consequently, CAD risk.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 it