CYP2C19、P2Y12基因多态性与缺血性脑卒中患者氯吡格雷抵抗的相关性研究

Association between CYP2C19,P2Y12 Genetic Polymorphisms and Clopidogrel Resistance in Ischemic Stroke Patients

目的：考察CYP2C19、P2Y12受体的基因多态性与氯吡格雷抵抗的相关性研究.方法：96例中国缺血性脑卒中患者持续服用氯吡格雷75 mg,收集全血提取DNA,采用Sequenom MassARRAY iPLEX（R）基因型分析技术进行CYP2C19＊ 2（681G＞A,rs4244285）、CYP2C19＊3（636 G＞A,rs4986893）及P2Y12受体（52G＞T,rs6809699） （744T＞C,rs2046934）4个SNPs的基因型分析.采用二磷酸腺苷（ADP）诱导光比浊法测定血小板聚集功能.采用Chi-square检验或Fisher确切概率法分析相关性.结果：患者分为氯吡格雷抵抗（CR）组与非抵抗组,CYP2C19＊ 2（rs4244285）及P2Y12受体（rs2046934）基因型分布在两组间的差异有统计学意义（P=0.027,P=0.034）.其中,CYP2C19＊2 GA＋ AA基因型为CR发生的风险因素（OR=2.607,95％CI：1.062～6.399）.CYP2C19＊3（rs4986893）及P2Y12受体（rs6809699）基因型分布在两组比较中差异无统计学意义（P＞0.05）.结论：在中国缺血性脑卒中患者中,CYP2C19＊2（rs4244285） GA＋ AA型与氯吡格雷抵抗的发生密切相关,该基因型检测将有助于指导氯吡格雷的临床合理应用.

Objective：To investigate the correlation between CYP2C19 and P2Y12 genetic polymorphisms and platelet response in ischemic stroke patients treated with clopidogrel.Methods：Totally 96 Chinese ischemic stroke patients were prospectively enrolled with clopidogrel （75 mg daily） as the antiplatelet.agent.Genotyping was performed using a custom Sequenom MassARRAY iPLEX（R）platform.Platelets were stimulated by 10 μ mol · L-1 ADP.Platelet aggregation response was measured using a BioData PAP-4 platelet aggregometer.The correlations were evaluated by Chi-square test or Fisher＇ s exact test.Results：The genotype frequencies of CYP2C19 ＊ 2 genetic polymorphisms （rs4244285） and P2Y12 genetic polymorphisms （rs2046934） were significantly different between clopidogrel resistance and non-resistance groups （P =0.027 ; P =0.039）.Especially,CYP2C19 ＊ 2 （rs4244285） GA ＋ AA genotype was correlated with an increased risk of clopidogrel resistance （OR =2.067,95% CI：1.062-6.399）.However,no differences in the genotype frequencies of the CYP2C19 ＊ 3 （rs4986893） and P2Y12 （rs6809699） genetic polymorphisms were detected between the clopidogrel resistance and non-resistance groups （P 〉 0.05）.Conclusion：A considerable fraction of the Chinese ischemic stroke patients is clopidogrel resistant,which might be correlative with CYP2C19 ＊ 2 （rs4244285） GA ＋ AA genetic polymorphisms.