The risk of coronary thrombosis with cyclo‐oxygenase‐2 inhibitors does not vary with polymorphisms in two regions of the cyclo‐oxygenase‐2 gene
Bibliographic record
Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The risk of cardiovascular events with non‐steroidal anti‐inflammatory drugs (NSAIDs) varies with individual drugs and with dosage. Little is known about other factors that can modify risk. • Polymorphisms of the COX‐2 gene conceivably could alter the risk of myocardial infarction and also the risk from NSAIDs. WHAT THIS STUDY ADDS • Two common polymorphisms of the COX‐2 gene, rs 20417 (G > C) and rs 5275 (T > C), were not associated with variation in the risk of acute coronary syndrome, and individually did not alter the risk associated with use of NSAIDs. • Haplotype analysis identified a trend to protection against NSAID‐related cardiovascular risk with the ‘low risk’ haplotype, but the effect was weak and if confirmed, the clinical utility would be limited. AIMS To investigate whether polymorphisms of the cyclo‐oxygenase‐2 (COX‐2) gene modify the adverse cardiovascular effects of COX‐2 inhibitors. METHODS A case control study was conducted in the Hunter Region of New South Wales, Australia. Cases (n= 460) were hospitalized with acute coronary syndrome (ACS). Controls (n= 640) were recruited from the electoral rolls. Structured interviews gathered information on variables including recent ingestion of non‐steroidal anti‐inflammatory drugs (NSAIDs). Targeted genotyping of rs 20417(G > C) and rs5275 (T > C) polymorphisms was performed by real‐time polymerase chain reaction using allele‐specific probes RESULTS Ingestion of any NSAID in the week prior to interview was associated with an elevated risk for ACS: adjusted odds ratio 1.8 (1.2, 2.5). The rs 20417 and rs 5275 polymorphisms were not singly associated with risk for ACS: adjusted odds ratios 1.1 (0.80, 1.5) and 1.2 (0.88, 1.5), respectively. Individually, the polymorphisms did not modify the risk of ACS with the drugs. When analyses were conducted by haplotype, the adjusted odds ratio with celecoxib or rofecoxib in individuals who had one or two copies of the ‘low risk’ haplotype (no GT) was 1.2 (0.29, 5.0), compared with 2.1 (1.1, 4.0) with the ‘high risk’ haplotype (one or two copies of GT). CONCLUSIONS We found little evidence of a gene/drug interaction. We found a statistically non‐significant trend toward a lower risk of coronary events with NSAIDs in the presence of the ‘low risk’ haplotype. Even if confirmed, the clinical utility of the finding would be limited as this haplotype is carried by a minority of the population.
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".