摘要
目的 探讨急性脑梗死患者氯吡格雷抵抗与CYP2C19 基因多态性和血小板反应性的关系.方法 收集2015年4月至2016年4月北京天坛医院脑梗死患者474例.测定CYP2C19基因型,根据基因型分为野生型组、突变杂合型组及突变纯合型组.使用血栓弹力图检测二磷酸腺苷（ADP）诱导的血小板聚集抑制率（ADP%）和血小板反应性指标,并根据ADP%是否〈30%将患者分为氯吡格雷抵抗组（CR组）和非抵抗组,比较两组患者CYP2C19基因型分布情况及血栓弹力图各指标的变化.采用Logistic回归分析,分析氯吡格雷抵抗的危险因素.结果 纳入的474例患者中,根据CYP2C19基因分型分为3组：野生型组204例（43.04%）,突变杂合型组204例（43.04%）及突变纯合型组66例（13.92%）.CR组与非抵抗组CYP2C19基因型分布构成差异有统计学意义（χ^2=6.658,P=0.036）.CR组血栓弹力图血凝块形成角[Angle（α）]值（68.87°±5.47°）和血栓弹力图最大振幅（MA）值（66.77±6.25） mm均高于非抵抗组[（66.55±6.05）°和（63.30±5.66） mm],t值分别为2.199和3.387,P值分别为0.029和0.001.Logistic回归分析显示,Angle（α）比值比（OR）为1.028,95%可信区间为0.929~1.137（P=0.595）;MA OR为 1.561,95%可信区间为 0.785~0.970（P=0.012）.结论 CYP2C19基因突变的急性脑梗死患者使用氯吡格雷抗血小板聚集的作用降低.CYP2C19突变型等位基因是氯吡格雷抵抗的危险因素.血栓弹力图中Angle（α）值和MA值是诊断氯吡格雷抵抗的危险因素,当患者的Angle（α）值和MA值升高时,提示发生氯吡格雷抵抗的风险增高.MA值作为氯吡格雷抵抗的预测与筛查工具有一定的价值.
Objective To study the effect of clopidogrel on different CYP2C19 genotypes and platelet reactivity in acute cerebral infarction patients with antiplatelet aggregation.Methods Four hundred and seventy-four cases of cerebral infarction patients in Beijing Tiantan Hospital Affiliated to Capital Medical University from April 2015 to April 2016 were collected.CYP2C19 genotype was determined,and the genotype was divided into the wild type group,the heterozygous type group and the mutant homozygous group.Platelet aggregation inhibition rate（ADP%） and platelet reactivity index induced by ADP were detected.Patients were divided into clopidogrel resistance group（group CR） and non resistant group according to whether ADP% was less than 30.SPSS 16.0 statistical software was used for statistical analysis,the comparison between groups using independent samples t test,chi square test and multivariate analysis using Logistic regression analysis,when P〈0.05 difference was statistically significant.Results Among the 474 patients,204 cases（43.04%） were divided into wild-type group,and 204（43.04%） and 66（13.92%） were divided into the mutant heterozygous group and mutant homozygous group.In Chi square test analysis,clopidogrel resistance group and non resistance group CYP2C19 genotype distribution was significantly different（χ^2=6.658,P=0.036）.CR group angle（α） values（（68.87±5.47）°） and MA（（66.77±6.25） mm） were higher than that of CS group （（66.55±6.05）° and （63.30±5.66） mm,t=2.199,3.387,P=0.029,0.001）.The multivariate logistic regression analysis showed that OR of angle level was 1.028,95%CI was 0.929-1.137 （P=0.595）;OR of Ma level was 1.561,95%CI was 0.785-0.970 （P=0.012）.Conclusion The effect of clopidogrel on platelet aggregation in patients with acute cerebral infarction is decreased by CYP2C19 gene mutation.CYP2C19 mutant allele is a risk factor for clopidogrel resistance.Angle （α） value and MA value are the risk factors for the diagnosis of CR in the patients with acute cerebral infarction,and the risk of clopidogrel resistance increased when the patients′ Angle （α） value and the value of MA increased.MA value as a predictor of CR and the screening tool has a certain value.
出处
《中国综合临床》
2017年第5期424-428,共5页
Clinical Medicine of China
