title: Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis.
abstract: OBJECTIVE
  Recurrent ischemic events in Chinese patients with symptomatic extracranial or intracranial stenosis caused by aspirin or clopidogrel resistance are well known. We aimed to identify the contribution of genetic variants to the events.
  
  
  METHODS
  Patients with symptomatic extracranial or intracranial stenosis receiving dual antiplatelet treatment for at least 5 days were enrolled in this study. The primary endpoint was a composite of ischemic events, including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality. Twenty-four single nucleotide polymorphisms (SNPs) were assessed and genotyped. The clinical characteristics of enrolled patients were collected from medical records. The influence of genetic polymorphisms on the recurrent ischemic events of the patients was examined.
  
  
  RESULTS
  A total of 377 patients were included. During a 12-month follow-up, the composite primary endpoint was observed in 64 patients. The CYP2C19*3 (rs4986893) may increase the occurrence of the primary composite endpoint (OR = 2.56, 95 % CI = 1.29-5.10, P = 0.007), and the mutation of CES1 rs8192950 was associated with the decreased recurrence of ischemic events (OR = 0.53, 95 % CI = 0.30-0.94, P = 0.029). The other SNPs that were tested did not have statistically significant associations with the composite endpoint.
  
  
  CONCLUSIONS
  For Chinese patients with symptomatic extracranial or intracranial stenosis treated with clopidogrel, CYP2C19*3 mutation was associated with an increased risk of ischemic events, and the mutation of rs8192950 in CES1 is associated with a decreased risk of recurrent ischemic events. Testing these two SNPs could be of value in the identification of patients at risk for recurrent ischemic events.
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.|Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Pharmacy, Western New England University, Springfield, MA, 01109, USA.
authors.forename: Shusen
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Zhongrong
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China. mingzhao@bjmu.edu.cn.|Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. mingzhao@bjmu.edu.cn.|College of Pharmaceutical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing, 100069, People's Republic of China. mingzhao@bjmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China. sqpeng@bjmu.edu.cn.|College of Pharmaceutical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing, 100069, People's Republic of China. sqpeng@bjmu.edu.cn.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D000077144:Clopidogrel; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007511:Ischemia / Q000235:genetics* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; D013988:Ticlopidine; D001241:Aspirin
keywords: Aspirin; CES1; CYP2C19; Clopidogrel; Ischemic; Stenosis