Abstract 2646: Haptoglobin 2 Allele Associates with Symptomatic Carotid Stenosis and Major Cardiovascular Events
Bibliographic record
Abstract
Objectives: Haptoglobin (Hp) is a plasma protein which binds free hemoglobin (Hb) protecting tissues from iron-induced oxidative damage and promoting Hb clearance via macrophage CD163 receptor. There are two common alleles for Hp (Hp 1 and Hp 2), which influence it’s capacity to bind Hb and induce downstream signaling via CD163+ macrophages. We have previously shown that the CD163-heme oxygenase-1 (HO1) pathway is upregulated in symptomatic carotid stenosis (CS) and other groups have associated the Hp 2-2 genotype with cardiovascular complications in diabetics. Here, our objective was to study whether Hp polymorphism influences the risk of symptomatic CS and major cardiovascular events in the general population. Methods: We genotyped Hp polymorphism in 90 patients with a high-grade CS (≥ 70%) from Helsinki Carotid Endarterectomy Study (HeCES) and in 1426 individuals with carotid ultrasound examination data from the Health 2000 Survey, an epidemiological cross-sectional health survey carried out in Finland in the year 2000. Results: In the Health 2000 population, the Hp genotype frequencies were 0.170 (Hp 1-1), 0.445 (Hp 1-2) and 0.386 (Hp 2-2) consistent with Hardy-Weinberg equilibrium and with those reported from caucasian populations. In the CS patients, the genotype frequencies were skewed towards the Hp 2-2 genotype but not significantly. However, among the patients with symptomatic CS (ipsilateral TIA or stroke), the frequency of Hp 2-2 genotype was significantly higher than in the control population (0.528 vs 0.386, P =0.044). Hp genotypes correlated with HO1 protein expression in the plaque (r=0.46, P = 0.038) but not with iron. In the Health 2000 population, Hp 2 allele was associated with an increased risk of major cardiovascular events (major coronary heart disease event, ischemic stroke or TIA; 13.3% vs 8.3, P =0.032) and the increased risk was present regardless of diabetes. Hp 2 allele was not associated with carotid IMT or presence of plaques. Conclusions: Hp 2 allele associates with the risk of symptomatic CS and major ischemic cardiovascular events. This is likely due to the defective ability of Hp 2 to block oxidative reactions mediated by iron/heme, to clear free Hb present in intraplaque hemorrhages as well as the effects of the Hb-Hp 2 complex on intracellular signaling cascades via the CD163 receptor.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".