Effect of apolipoprotein E, peroxisome proliferator-activated receptor alpha and lipoprotein lipase gene mutations on the ability of fenofibrate to improve lipid profiles and reach clinical guideline targets among hypertriglyceridemic patients.
Bibliographic record
Abstract
Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARalpha) agonist which regulates the transcription of genes encoding proteins involved in triglyceride (TG)-rich lipoproteins and lipoprotein lipase (LPL) metabolism. The aim of the present study was to investigate the relation between TG-related parameters considered in different clinical guidelines used in industrialized countries for the management of lipid disorders (namely fasting plasma TG, high density-lipoprotein cholesterol (HDL-C), non-HDL-C concentrations and total-C/HDL-C ratio) and the presence of LPL-null (P207L), LPL-defective (D9N), PPARalpha -L162V, apolipoprotein (apo) E and PPARgamma-P12A gene mutations, in a sample of 292 hypertriglyceridemic subjects treated with fenofibrate for 3 months. Although fenofibrate induced a decrease in plasma TG level and an increase in HDL-C level in all studied genotypes, mutation-specific differences were observed. After adjustment for age, gender, body mass index and the presence of apo E2 genotype, the LPL-P207L mutation was associated with residual post-treatment hypertriglyceridemia [TG > 2.0 mmol/l, odds ratio (OR) = 3.07, P = 0.005] and total-C/HDL-C ratio > 5 (OR = 2.68; P = 0.03). This effect was significantly related to higher plasma TG concentrations at baseline among carriers of a LPL-null mutation. Compared to apo E3 and E4 variants, the apo E2 allele was associated with a better response to fenofibrate on all lipid parameter, especially among PPARalpha -L162V carriers, whereas the simultaneous presence of apo E2 and PPARalpha -L162V tended to improve fenofibrate response among LPL-P207L heterozygotes. Finally, the LPL-D9N and PPARgamma -P12A mutations did not affect fenofibrate lipid-lowering action. This study suggests that frequent genetic variations in genes encoding proteins involved in TG-rich lipoprotein metabolism could modulate the response to fenofibrate treatment, as defined in clinical guidelines.
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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 | 0.000 |
| Science and technology studies | 0.000 | 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 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".