Platelet receptor Gene (P2Y12, P2Y1) and platelet glycoprotein Gene (GPIIIa) polymorphisms are associated with antiplatelet drug responsiveness and clinical outcomes after acute minor ischemic stroke.

PURPOSE

Patients with minor ischemic stroke (MIS) are at high risk of recurrent ischemic stroke (RIS). The aim of this study was to evaluate the effects of platelet receptor gene (P2Y12, P2Y1) and glycoprotein gene (GPIIIa) polymorphisms, as well as their interactions, on antiplatelet drug responsiveness and clinical outcomes in patients with acute MIS.

METHODS

We prospectively enrolled 426 patients with acute MIS who had been receiving combined aspirin and clopidogrel treatment for at least 3 months. Prevalence of seven variants in P2Y12, P2Y1, and GPIIIa genes were examined using mass spectrometry. Gene-gene interactions were evaluated using generalized multifactor dimensionality reduction (GMDR) analysis. Antiplatelet drug responsiveness was assessed by platelet aggregation assay. All patients were followed for 90 days. Primary outcomes were defined as a composite of RIS, myocardial infarction (MI), and death.

RESULTS

The incidence of primary outcomes was 10.8% (46/426; 40 had RIS, 2 died, and 4 had MI) during the first 90 days after stroke. No significant differences were found regarding genotype frequencies of the seven variants between those with and without incidence of primary outcomes. However, we observed significant gene-gene interaction between rs16863323 and rs2317676 polymorphisms. The high-risk interactive genotypes were independently associated with poor antiplatelet drug responsiveness and increased risk of primary outcomes.

CONCLUSION

Responsiveness to antiplatelet drugs and the risks for adverse clinical events in this MIS cohort appear to be multifactorial since the outcomes were not mediated by single gene polymorphisms.