Association of platelet ADP receptor variant rs1371097 with inadequate platelet response to aspirin in Indian...

On-aspirin platelet reactivity, wherein patients show sub-optimal or no response to antiplatelet therapy, occurs in 5-60% of subjects. The genetic etiology of such reactivity in patients with vascular diseases, especially ischemic stroke in the Indian population, is unknown. This study aimed to examine the genetic variations in the pathways of platelet aggregation and aspirin metabolism that could predict aspirin response.

This is a prospective cohort study, which included 293 ischemic stroke patients on 150 mg aspirin for over 7 days. Platelet aggregation was assessed using light transmission aggregometry with 10 µM ADP and 0.5 mM arachidonic acid as agonist. After excluding patients with serum salicylic acid levels < 30 µg/mL, 230 individuals were analyzed. Candidate gene variants in COX1, COX2, GpIIb/IIIa, P2RY1, PEAR1, ITGB3, and UGT1A6, were genotyped using PCR-RFLP or allelic discrimination assays.

The T allele of P2RY1 (rs1371097 C > T) was significantly associated with inadequate platelet response with an odds ratio of 1.71 (95% CI: 1.122-2.61; p = 0.0131). Carriers of this allele had a 3.46-fold increased risk of inadequate response after adjustment for age and gender.

The P2RY1 (rs1371097 C > T) variant may be a potential genetic marker for inadequate response to aspirin in Indian ischemic stroke patients.