Determinants of Lipid Level Variability in French-Canadian Children With Familial Hypercholesterolemia
Bibliographic record
Abstract
The wide variability in the biochemical expression of familial hypercholesterolemia (FH) is only partly explained by mutational heterogeneity in the low density lipoprotein receptor (LDLR) gene. In the current study, we measured this biochemical variability in a group of children heterozygous for the >15-kb LDLR gene deletion (n=67) and examined the contribution of apolipoprotein (apo) E and B allelic variations to this phenotypic variability. Variances of total cholesterol (TC), LDL-C, and apoB concentrations and of the ratio of TC to high density lipoprotein cholesterol (HDL-C) were increased in FH subjects compared with controls. However, after taking the means into account, the coefficients of variation showed that the variability of LDL-C and apoB concentrations was smaller for FH than for controls and that the variability of TC and of the ratio TC to HDL-C was similar between both groups. The epsilon2/3 genotype was associated with lower mean TC, LDL-C, and apoB concentrations in FH. The magnitude of this effect was smaller in controls than in FH. Indeed, the percentages of total variance of TC, LDL-C, and apoB attributable to the apoE locus were 19.9%, 18.1%, and 11.8%, respectively, in FH cases and 5.9%, 7.4%, and 6.0%, respectively, in controls. We did not detect any effect of the apoB insertion/deletion polymorphism on lipid traits in FH children. However, in controls, we observed a strong interaction between apoE and apoB genotypes on apoB concentrations and on TC to HDL-C ratios. Our study reemphasizes the important role of apoE in lipid metabolism and illustrates that the effects of allelic variations on lipid traits are context dependent.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".