Abstract 567: Genetic and Clinical Heterogeneity of Marked High Density Lipoprotein Deficiency
Bibliographic record
Abstract
Aim: Our goal was to assess the population prevalence, genetics and clinical phenotypes of subjects with marked HDL deficiency. Methods: 200 subjects (26% female, mean age 52 years) with serum HDL-C < 20 mg/dL, fasting triglycerides (TG) < 600 mg/dL, C reactive protein (CRP) < 10 mg/L, myeloperoxidase (MPO) < 1000 pmoles/L, HbA1c < 8.0%, liver transaminases < 120 U/L, and not taking anabolic steroids were studied. Lipids, inflammation markers, liver enzymes, and HDL particles were assessed; and sequencing of 31 lipid metabolism genes including ABCA1, APOA1, LCAT , and LPL was done. Results: HDL-C < 20 mg/dl was observed in 473 (0.35%) men (n=135,912) and 140 (0.089%) women (n=160,964) in our population over one year. In this low HDL group, 6.4% had elevated CRP, 4.4% had abnormal liver function, 4.2% had elevated HbA1c, 1.0% had elevated MPO, 0.5% had elevated TG, and 11.5% of men were taking anabolic steroids. These subjects were excluded. The 200 subjects studied had plasma values of LDL-C 102, HDL-C 15, TG 239, and apoA-I 76 mg/dL, with a marked deficiency of very large and large α-1 and α-2 HDL. ABCA1 mutations were found in 38 subjects (19.0%; 29 heterozygotes, 6 compound heterozygotes, 3 homozygotes). APOA1 mutations were found in 10 subjects (5.0%; 9 heterozygotes, 1 homozygote). LCAT mutations were found in 17 subjects (8.5%; 13 heterozygotes, 3 compound heterozygotes, 1 homozygote). In addition, 11 subjects (5.5%) had the LPL N318S variant, and 13 subjects (6.5%) had the ABCA1 c.-279 C>G variant. Premature coronary heart disease (CHD) was observed in some subjects with ABCA1 and APOA1 mutations. Neuropathy was observed in some subjects with ABCA1 mutations, and kidney failure was observed in the subject with the homozygous LCAT mutation. Conclusions: Marked HDL deficiency occurred in 0.2% of our population and can be associated with liver disease, inflammation, diabetes, severe hypertriglyceridemia, and the use of anabolic steroids. In the absence of these conditions, mutations in ABCA1, APOA1, or LCAT were found in 32% of subjects studied. Premature CHD was seen in some subjects with ABCA1 or APOA1 mutations, neuropathy was seen in some subjects with ABCA1 mutations, and kidney failure was observed in some subjects with LCAT mutations.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.003 | 0.001 |
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".