title: Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting.
abstract: OBJECTIVE
  Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.
  
  
  METHODS
  Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.
  
  
  RESULTS
  A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03-2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10-3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12-3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.
  
  
  CONCLUSIONS
  PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events.
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.|Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, China.
authors: Xiao-Qing
authors: XQ
authors: Li
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Ning
authors: N
authors: Ma
authors: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Xin-Gang
authors: XG
authors: Li
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Bo
authors: B
authors: Wang
authors: College of Pharmacy, Western New England University, Springfield, Massachusetts, United States of America.
authors: Shu-Sen
authors: SS
authors: Sun
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Feng
authors: F
authors: Gao
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Da-Peng
authors: DP
authors: Mo
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Li-Gang
authors: LG
authors: Song
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Xuan
authors: X
authors: Sun
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Lian
authors: L
authors: Liu
authors: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Xing-Quan
authors: XQ
authors: Zhao
authors: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Yi-Long
authors: YL
authors: Wang
authors: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Yong-Jun
authors: YJ
authors: Wang
authors: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Zhi-Gang
authors: ZG
authors: Zhao
authors: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
authors: Zhong-Rong
authors: ZR
authors: Miao
mesh_terms: D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D012008:Recurrence; D015607:Stents
chemical_list: C548576:P2RY12 protein, human; D058925:Receptors, Purinergic P2Y12; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human