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

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.