Disparate Associations of a Functional Promoter Polymorphism in <b>PCK1</b> With Carotid Wall Ultrasound Traits
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32), encoded by PCK1, catalyzes the first committed step in gluconeogenesis. We previously showed that a -232C>G promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance. We hypothesized that this polymorphism would be associated with carotid atherosclerosis in a sample of 150 aboriginal Canadians. METHODS: Dependent variables were 2 distinct carotid traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and total carotid plaque volume (TPV) assessed using 3D ultrasound. RESULTS: Multivariate analysis showed significant but opposite associations of PCK1 genotype with these traits. Specifically, subjects with the PCK1-232G/G genotype had more carotid IMT (0.80+/-0.02 versus 0.73+/-0.03 mm; P=0.007) but less TPV (0.10+/-0.09 versus 0.38+/-0.13; P=0.03) than subjects with other genotypes. CONCLUSIONS: The findings connect the key enzyme in gluconeogenesis with atherosclerosis. The meaning of the opposing associations of PCK1 genotype with IMT and TPV is unclear; more work is required to confirm whether these might be distinct quantitative traits with different biological determinants.
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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".