Impact of IRS-1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing PCI
Bibliographic record
Abstract
Abstract Background insulin receptor substrate-1 (IRS-1) rs956115 is associated with vascular risk in patients with coronary artery disease (CAD) and concomitant diabetes. CYP2C19 rs4244285 modulates clopidogrel responsiveness and predicts outcome of CAD. We designed this study to explore the association between IRS-1 rs956115, CYP2C19 rs4244285, and platelet reactivity as well as 1-year outcome in patients with CAD undergoing percutaneous coronary intervention (PCI).Methods IRS-1 rs956115, CYP2C19 rs4244285 genotypes and platelet reactivity were assessed in 1611 post-PCI patients. Major adverse cardiovascular events (MACE) which were defined as a composite of cardiovascular death, myocardial infarction and ischemic stroke over 1-year were evaluated. One-way ANOVA was used to compare the platelet reactivity among different genotypes of rs956115 and rs4244285. Multivariable Cox proportional hazard model analysis was used to estimate the association between genotypes of rs956115 and rs4244285 and risk of MACE.Results At 1 month, patients with rs956115 CG genotype had significantly lower level of residual ADP-induced platelet aggregation (PLADP) than those with CC genotype. PLADP significantly increased with the number of rs4244285 A alleles. Patients with rs956115 CG or GG genotype had a 2.09-fold higher risk of MACE than those with CC genotype (adjusted HR=2.09; 95%CI:1.04-4.19; P=0.0376), and those with rs4244285 GA genotype had a 2.19-fold higher risk than GG homozygotes (adjusted HR=2.19; 95%CI:1.13-4.24; P=0.0200). There was no significant difference in risk between AA and GG homozygotes. No interaction between rs956115 and rs4244285 was observed. Conclusions In post-PCI patients, rs956115 GG/CG and rs4244285 GA genotypes were associated with 2.09- and 2.19-fold cardiovascular risks respectively at 1-year follow-up. The effect of rs956115 appeared to be independent of known clinical predictors, while that of rs4244285 GA could be mediated by lower clopidogrel response. Trial registration: Pharmacogenetic and Pharmacokinetic Study of Clopidogrel (PPSC), NCT01968499. Registered October 17, 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01968499?term=NCT01968499&draw=1&rank=1
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".