title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, The People's Hospital of Deyang City, 173 North Taishan Road, Deyang, Sichuan, 618000, China.
authors.forename: Xingyang
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325200, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The People's Hospital of Deyang City, 173 North Taishan Road, Deyang, Sichuan, 618000, China. 1842942576@qq.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325200, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Neurology, The People's Hospital of Deyang City, 173 North Taishan Road, Deyang, Sichuan, 618000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurology, Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, 325200, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fu
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12
keywords: Antiplatelet drugs resistance; Genetic variants; Minor ischemic stroke; Pharmacogenetics; Stroke recurrence