Variation in Niemann–Pick C1‐like 1 gene as a determinant of apolipoprotein B‐100 kinetics and response to statin therapy in centrally obese men
Bibliographic record
Abstract
OBJECTIVE: Niemann-Pick C1-like 1 protein (NPC1L1) plays a key role in lipoprotein metabolism. We examined the association of common genetic polymorphisms in NPC1L1 on apolipoprotein (apo) B-100 metabolism and the response to statin treatment in 37 men with central obesity. RESEARCH METHODS AND PROCEDURE: Very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL)-apoB kinetics were determined using stable isotope method. NPC1L1 genotypes (1735G > C, 25432A > C and 27677T > C) were determined by allele-specific methods. These three polymorphisms are defined as haplotype, namely 1735C-25432A-27677T, and was designated as 'haplotype 2'. RESULTS: Relative to non-2/2 haplotype (n = 23), subjects with the 2/2 haplotype (n = 14) had significantly increased plasma concentrations of total, LDL-cholesterol, and total apoB (P < 0.05). The fractional catabolic rate (FCR) of LDL-apoB was significantly lower in 2/2 subjects compared with non-2/2 subjects (P < 0.05), with an associated increase in LDL-apoB pool size in the former group. Sixteen subjects were then treated with 40 mg atorvastatin (6 weeks): 2/2 subjects (n = 8) had a significantly greater reduction in plasma concentrations of cholesterol and total apoB and in LDL-apoB pool size, as well as a greater increase in LDL-apoB FCR compared with non-2/2 subjects. There were no significant treatment-related between-haplotype differences in VLDL-apoB kinetics or in plasma concentrations of lathosterol and campesterol. CONCLUSION: Our data demonstrate that NPC1L1 2/2 haplotype was associated with variation in LDL-apoB metabolism and its response to statin therapy in centrally obese men, by a mechanism that did not involve changes in VLDL-apoB kinetics, nor cholesterol synthesis or absorption.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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) | 0.000 | 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 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".