Association of the COX-2 rs689466 genetic variant with aspirin resistance in patients with Ischemic heart disease

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Ischemic heart disease (n=120). Intervention: COX-2 rs689466 T/C genotype vs. COX-2 rs689466 T/T genotype. Primary outcome: Laboratory-defined aspirin resistance (arachidonic acid-induced aggregation ≥20%, ADP-induced aggregation ≥70%, and/or collagen-induced aggregation ≥70%) (OR 1.16, 95% CI 0.47–2.86, p=0.69).

Q: What does this research mean for the field?

The COX-2 rs689466 genetic polymorphism is not significantly associated with laboratory-defined aspirin resistance in patients with ischemic heart disease. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Mehak Batool; Nazish Saqlain; Asif Haleem Khan; Sidra Rasool

doi:10.12669/pjms.42.11.16321

October 15, 2026Pakistan Journal of Medical SciencesOpen Access

Association of the COX-2 rs689466 genetic variant with aspirin resistance in patients with Ischemic heart disease

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Key result

COX-2 rs689466 polymorphism shows no association with aspirin resistance in ischemic heart disease.

OR 1.16
95% CI 0.47–2.86
P=0.69
n=120

Why the study?

The prevalence of laboratory-defined aspirin resistance and its association with the COX-2 rs689466 polymorphism in Pakistani ischemic heart disease patients needed to be determined.

Is the COX-2 rs689466 genetic polymorphism associated with laboratory-defined aspirin resistance in Pakistani patients with ischemic heart disease?

Key Points

To establish the prevalence of laboratory-defined aspirin resistance and determine its association with the COX-2 rs689466 polymorphism in patients with ischemic heart disease.
Assessed laboratory-defined aspirin resistance using light transmission aggregometry with arachidonic acid (≥ 20%), ADP (≥ 70%), and collagen (≥ 70%) agonists.
Genotyped the COX-2 rs689466 polymorphism using DNA extraction followed by a polymerase chain reaction-based protocol.
Laboratory-defined aspirin resistance was present in 70 patients (58.3%).
Genotypic frequencies of COX-2 rs689466 were 75.0% for T/T, 21.7% for T/C, and 3.3% for C/C, showing no significant difference between resistant and non-resistant groups (p = 0.715).
No significant association was detected across genetic models, with the codominant model for the T/C genotype yielding an OR of 1.16 (95% CI: 0.47–2.86, p = 0.69) compared to T/T.

Study Design

Type

Cross-Sectional (n=120)

Multicenter

No

Structured PICO

Is the COX-2 rs689466 genetic polymorphism associated with laboratory-defined aspirin resistance in Pakistani patients with ischemic heart disease?

P

Population

120 adult Pakistani patients with ischemic heart disease (mean age 56.9 years, 30.8% female) receiving aspirin therapy for at least 7 days.

E

Exposure

Aspirin therapy for at least 7 days prior to enrollment, stratified by COX-2 rs689466 polymorphism genotypes (T/T, T/C, C/C).

O

Outcome

Association of COX-2 rs689466 genetic polymorphism with laboratory-defined aspirin resistance, determined by Light Transmission Aggregometry (defined as meeting any one threshold: arachidonic acid-induced aggregation ≥20%, ADP-induced aggregation ≥70%, and/or collagen-induced aggregation ≥70%).surrogate

Main Result

Odds Ratio: 1.16 (95% CI 0.47–2.86)

p-value: p=0.69

Despite a 58.3% prevalence of laboratory-defined aspirin resistance in this Pakistani cohort with ischemic heart disease, the COX-2 rs689466 genetic polymorphism showed no significant association with aspirin responsiveness, underscoring the multifactorial nature of aspirin resistance.

Limitations

Small sample size (n=120)
Single ethnic patient group (Pakistani Punjabi origin) limiting generalizability
Aspirin resistance evaluated using only light transmission aggregometry without other platelet function assays
Analysis limited to a single genetic variant (COX-2 rs689466)
Medication adherence confirmed by self-report and prescription review rather than objective measures like pill counts or serum salicylate levels
Confounding comorbidities (hypertension and diabetes mellitus), concomitant drug use, dietary influences, and pharmacokinetic differences were not separately analyzed between groups
Small sample size and single ethnic patients' group restricting applicability
Platelet function evaluated using only light transmission aggregometry without other platelet function assays
Analysis limited to a single genetic variant (COX-2 rs689466) without assessing other genetic and non-genetic factors
Differential distribution of confounders like hypertension and diabetes mellitus between resistant and non-resistant groups was not separately analyzed

Implication

No association with COX-2 rs689466; leaves open multifactorial etiology of aspirin resistance and requires larger prospective studies.

Abstract

Objectives: To determine the prevalence of laboratory-defined aspirin resistant cases and to find the association of COX-2 rs689466 polymorphism with aspirin resistance (AR) in Pakistani ischemic heart disease (IHD) patients. Methodology: This cross-sectional analytical study was carried out at UHS and PGMI, Lahore from February 2025 to January 2026, involving 120 adult IHD patients who had been on aspirin therapy for the last 07-days. Laboratory-defined AR was determined using Light transmission Aggregometry, where resistance was defined by aggregation criteria with agonists like Arachidonic acid (≥ 20%), ADP (≥ 70%), and Collagen (≥ 70%). Genotyping for the COX-2 rs689466 polymorphism was performed using the phenol chloroform method for extraction of DNA, followed by a Polymerase Chain Reaction (PCR) based protocol. Data was analyzed using SPSS version-24. Results: The laboratory defined aspirin resistance was observed in 70(58.3%) patients. Genotype analysis for COX-2 rs689466 showed the T/T genotype was the most common in the case group (73%), followed by T/C (23%), and the rare C/C genotype (4%). No significant association was found between the COX-2 rs689466 polymorphism and aspirin resistance under any genetic model (codominant, dominant, recessive, over-dominant, or log-additive). For instance, the codominant model for the T/C genotype yielded an odds ratio (OR) of 1.16 (95% CI: 0.47–2.86, p = 0.69) compared to T/T. Conclusion: Despite a high incidence of laboratory-defined aspirin resistance among this cohort, the COX-2 rs689466 polymorphism was not significantly associated with Aspirin resistance. These findings predict its multifactorial nature and suggest the need for individualized antiplatelet therapy.

Discussion

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Cite This Study

Batool et al. (2026) conducted a cross-sectional in Ischemic heart disease (n=120). COX-2 rs689466 T/C genotype vs. COX-2 rs689466 T/T genotype was evaluated on Laboratory-defined aspirin resistance (arachidonic acid-induced aggregation ≥20%, ADP-induced aggregation ≥70%, and/or collagen-induced aggregation ≥70%) (OR 1.16, 95% CI 0.47–2.86, p=0.69). The COX-2 rs689466 polymorphism showed no significant association with aspirin resistance (58.3% prevalence) in ischemic heart disease patients (T/C vs T/T OR 1.16, 95% CI 0.47–2.86, p=0.69).

synapsesocial.com/papers/6ae28e75cbadf70daf6c4262 https://doi.org/10.12669/pjms.42.11.16321

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Association of the COX-2 rs689466 genetic variant with aspirin resistance in patients with Ischemic heart disease

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Association of the COX-2 rs689466 genetic variant with aspirin resistance in patients with Ischemic heart disease

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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