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缺血性脑梗死患者氯吡格雷抵抗的危险因素及其与基因rs1045642多态性的相关性

Risk factors for clopidogrel resistance in patients with ischemic cerebral infarction and the correlation with gene rs1045642 polymorphism.

作者信息

Su Jun-Feng, Hu Xiao-Hui, Li Cheng-Yan

机构信息

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Department of Neurology, Jingzhou Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jingzhou, Hubei 434020, P.R. China.

出版信息

Exp Ther Med. 2015 Jan;9(1):267-271. doi: 10.3892/etm.2014.2058. Epub 2014 Nov 10.

Abstract

The aim of the present study was to examine clopidogrel resistance (CR) in patients with ischemic cerebral infarction and its potential association with a single nucleotide polymorphism (SNP; rs1045642) in the gene. Patients with ischemic cerebral infarction received clopidogrel (75 mg/day) for 7 days and were then subjected to a turbidimetric assay to determine platelet aggregation. Patients were then divided into a CR group and a clopidogrel-sensitive (CS) group. Demographic and clinical data between the two groups were compared. Multivariate logistic regression analysis was performed to determine independent risk factors of CR. PCR products were sequenced to assess rs1045642 SNP genotype and allele frequencies in each group. In total, 303 patients were enrolled in the study; this included 51 CR cases (16.83%) and 252 CS cases (83.17%). Several parameters, including hypertension, diabetes, calcium channel blocker (CCB), β-receptor blocking agent and proton pump inhibitor use, and creatinine, fasting blood glucose, homocysteine (HCY), high-sensitivity C-reactive protein (hs-CRP) and triglyceride levels were significantly higher in the CR group than in the CS group. Diabetes, hs-CRP-increased use of CCBs, and use of β-blockers were found to be independent risk factors for CR. However, gene rs1045642 polymorphism was not found to be an independent risk factor for CR. In conclusion, CR in ischemic stroke patients is associated with several independent risk factors, including diabetes, hs-CRP-increased use of CCBs, and use of β-blockers. However, gene rs1045642 polymorphism has no correlation with CR.

摘要

本研究旨在检测缺血性脑梗死患者的氯吡格雷抵抗(CR)情况及其与该基因单核苷酸多态性(SNP;rs1045642)的潜在关联。缺血性脑梗死患者接受氯吡格雷(75毫克/天)治疗7天,然后进行比浊法检测以确定血小板聚集情况。随后将患者分为CR组和氯吡格雷敏感(CS)组。比较两组的人口统计学和临床数据。进行多因素逻辑回归分析以确定CR的独立危险因素。对PCR产物进行测序以评估每组中rs1045642 SNP的基因型和等位基因频率。本研究共纳入303例患者;其中包括51例CR病例(16.83%)和252例CS病例(83.17%)。CR组的几个参数,包括高血压、糖尿病、钙通道阻滞剂(CCB)、β受体阻滞剂和质子泵抑制剂的使用情况,以及肌酐、空腹血糖、同型半胱氨酸(HCY)、高敏C反应蛋白(hs-CRP)和甘油三酯水平均显著高于CS组。糖尿病、hs-CRP升高、CCB的使用增加以及β受体阻滞剂的使用被发现是CR的独立危险因素。然而,该基因rs1045642多态性未被发现是CR的独立危险因素。总之,缺血性中风患者的CR与几个独立危险因素相关,包括糖尿病、hs-CRP升高、CCB的使用增加以及β受体阻滞剂的使用。然而,该基因rs1045642多态性与CR无关。

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