K45R variant of squalene synthase increases total cholesterol levels in two study samples from a French Canadian population
Bibliographic record
Abstract
Squalene synthase is an important component of the cholesterol biosynthetic pathway, and inhibitors of this enzyme have been shown to lower plasma cholesterol levels. Previously, we sequenced the squalene synthase gene, FDFT1 (farnesyl-diphosphate farnesyltransferase), and identified several SNPs, including a nonsynonymous variant, rs11549147:A>G (K45R). To examine the possible association of K45R with plasma lipid traits, we tested 887 individuals from 149 families from the founder population of Saguenay-Lac St. Jean (SLSJ), Quebec. K45R was associated with increased total cholesterol (TC) (P=0.035) and non-high-density lipoprotein cholesterol (non-HDL-C) (P=0.01). These results were replicated in an independent sample of unrelated individuals (P=0.0008 for TC, P=0.004 for non-HDL-C). This SNP also influenced low-density lipoprotein cholesterol (P=0.042) and HDL-C (P=0.025) in the family-based sample, and triglycerides (TG) (P=0.007) in the unrelated subjects. The lysine (K) in codon 45 is conserved across 11 mammals and lies in a potential exonic splicing enhancer (ESE) site. These results suggest that this coding variant in the squalene synthase gene influences plasma cholesterol levels, possibly by affecting the intracellular production of cholesterol.
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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 | 0.000 | 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".