title: Influence of CYP2C19 polymorphisms on platelet reactivity and clinical outcomes in ischemic stroke patients treated with clopidogrel.
abstract: CYP2C19 genetic polymorphisms influence clopidogrel response and clinical outcomes of cardiovascular disease. However, data on their relationship in stroke patients are scarce. We aimed to investigate the influence of CYP2C19 polymorphisms on platelet reactivity and clinical outcomes in ischemic stroke patients treated with clopidogrel. A total of 211 patients were enrolled. All patients were given clopidogrel treatment and underwent CYP2C19 genotyping and platelet function testing by flow cytometry including adenosine diphosphate-induced platelet aggregation (ADP-PAg) and platelet activation markers (PAC-1, CD62P and CD63). The modified Rankin Scale (mRS) was used and ischemic events were evaluated. A total of 129 (61.1%) of the 211 enrolled patients were carriers of CYP2C19 loss-of-function (LOF) alleles (*2, *3). After clopidogrel therapy for 7 days, the levels of ADP-PAg, PAC-1, CD62P and CD63 were higher in carriers than noncarriers. CYP2C19 carriage was associated with more frequent high residual platelet reactivity. CYP2C19 polymorphisms alone could explain 12.9%, 4.3%, 8.9% and 5.5% of the inter-individual variability of ADP-PAg, PAC-1, CD62P and CD63 after clopidogrel treatment, respectively. At 6-month follow-up, 38 (19%) patients were scored poor prognosis and 15 (7.6%) ischemic events were observed. Carriers had poorer prognosis than noncarriers (P=0.025). No significant association of CYP2C19 carriage with ischemic events was found. Multiple regression analysis showed that CYP2C19 carriage was an independent predictor of poor prognosis (odds ratio, 3.01; 95% confidence interval, 1.23-7.38; P=0.016). In conclusion, carriage of the CYP2C19 LOF allele has significant influence on clopidogrel response and prognosis in patients with ischemic stroke.
authors.affiliation: Department of Neurology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Qiu
authors.affiliation: Tianjin Key Laboratory of Urology, Tianjin Institute of Urology Medical University, Tianjin 300211, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Geratology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China; Tianjin Institute of Geratology, Tianjin 300211, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Urology, Tianjin Institute of Urology Medical University, Tianjin 300211, China.
authors.forename: Rui-Fa
authors.initials: RF
authors.lastname: Han
authors.affiliation: Department of Neurology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Xiao-Shuang
authors.initials: XS
authors.lastname: Xia
authors.affiliation: Department of Neurology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China. Electronic address: lixinsci@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002545:Brain Ischemia / Q000150:complications*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011379:Prognosis; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: Adenosine diphosphate (PubChem CID: 6022); CYP2C19; Clopidogrel; Clopidogrel (PubChem CID: 60606); Flow cytometry; Genetic polymorphism; Ischemic stroke; Platelet function tests