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

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 &lt; 30 µg/mL, 230 individuals were analyzed. Candidate gene variants in <i>COX1, COX2, GpIIb/IIIa, P2RY1, PEAR1, ITGB3</i>, and <i>UGT1A6</i>, were genotyped using PCR-RFLP or allelic discrimination assays. The T allele of <i>P2RY1</i> (rs1371097 C &gt; T) was significantly associated with inadequate platelet response with an odds ratio of 1.71 (95% CI: 1.122–2.61; <i>p</i> = 0.0131). Carriers of this allele had a 3.46-fold increased risk of inadequate response after adjustment for age and gender. The <i>P2RY1</i> (rs1371097 C &gt; T) variant may be a potential genetic marker for inadequate response to aspirin in Indian ischemic stroke patients. Platelets are tiny cells in the blood that normally stick together to form clots and stop bleeding. An ischemic stroke occurs when an abnormal blood clot blocks the flow of blood to a part of the brain. Aspirin, an antiplatelet drug, is widely used to prevent abnormal blood clots in patients with ischemic stroke. However, not all patients respond to aspirin as expected, thereby predisposing them to repeated strokes and other complications. In this study, Indian patients with ischemic stroke were investigated for how genetic differences affect their platelet response to aspirin. For this, we included 230 patients who had been taking aspirin for at least 7 days and measured their platelet response in the laboratory using the gold standard platelet function test. We also studied their DNA to know the effect of genetic variants which was reported in other world populations. Our findings showed that a genetic variant in the P2RY1 gene (rs1371097C &gt; T) was linked to 3.4 fold higher risk of experiencing inadequate response to aspirin, even after accounting for age, gender, etc. Surprisingly, other genetic variants which were examined did not reveal a significant effect. This finding is important because it can help to create algorithms to tailor treatments for each person. However, we suggest careful interpretation of our results and recommend larger genetic studies, such as those using Next Generation Sequencing, to find more variants specific to the Indian population. Ethics approval was obtained from the Institute Ethics Committee of NIMHANS (No. NIMHANS/86th IEC/2012) and experiments were conducted in compliance with the Institutional guidelines. All study participants signed a written informed consent form.