CYP2C19∗2∗3和CES1A2-816基因多态性与动脉粥样硬化型脑梗死氯吡格雷反应性的关系  

Relationship between CYP2C19∗2∗3 and CES1A2-816 Gene Polymorphism and Clopidogrel Response in Patients with Atherosclerotic Cerebral Infarction

作　　者：闫安[1] 初双宝 李春颖[2] YAN An;CHU Shuangbao;LI Chunying(Affiliated Hospital of Beihua University,Jilin 132011,China;Basic Medical College of Beihua University,Jilin 132013,China)

机构地区：[1]北华大学附属医院,吉林吉林132011 [2]北华大学基础医学院,吉林吉林132013

出　　处：《北华大学学报（自然科学版）》2020年第6期761-764,共4页Journal of Beihua University（Natural Science）

基　　金：吉林省教育厅科学技术研究项目(JJKH20190638KJ);吉林市科技创新发展计划项目(201851881).

摘　　要：目的探讨CYP2C19∗2∗3和CES1A2-816基因多态性与动脉粥样硬化型脑梗死患者的氯吡格雷反应性关系.方法前瞻性连续入组复发动脉粥样硬化型脑梗死患者96例,患者服用氯吡格雷75 mg/d,5 d后应用血栓弹力图测定血小板抑制率,并进行基因分型.CYP2C19∗2和CYP2C19∗3分为纯合野生型(GG)、杂合变异型(GA)、纯合变异型(AA);CES1A2-816分为纯合野生型(AA)、杂合变异型(AC)、纯合变异型(CC).记录患者1 a内终点事件发生情况.结果3种CYP2C19∗2∗3基因分型患者血小板抑制率的差异具有统计学意义(P<0.01),其中,快代谢型抑制率最高,慢代谢型抑制率最低.3种CES1A2-816基因分型患者的血小板抑制率差异具有统计学意义(P<0.01),其中,AA型抑制率最高,CC型抑制率最低.CYP2C19∗2∗3基因、CES1A2-816基因、BMI>26 kg/m^2是复发动脉粥样硬化型脑梗死患者血小板抑制率的独立影响因素.CYP2C19∗2∗3及CES1A2-816失功能等位基因携带者是主要终点事件的独立危险因素;年龄≥60岁也是主要终点事件的独立危险因素.结论携带CYP2C19∗2∗3及CES1A2-816失功能等位基因的复发动脉粥样硬化型脑梗死患者氯吡格雷反应性均降低,可导致复发动脉粥样硬化型脑梗死患者的主要终点事件风险增加.Objective To investigate the relationship between CYP2C19* 2* 3 and CES1A2-816 gene polymorphism and clopidogrel response in patients with recurrent atherosclerotic cerebral infarction.Method 96 patients with recurrent atherosclerotic cerebral infarction were enrolled, after taking clopidogrel 75 mg/d,thromboelastography was used to determine the platelet inhibition rate and genotyping after 5 days.CYP2C19* 2 and CYP2C19* 3 were divided into homozygous wild type(GG),heterozygous variant(GA),homozygous variant(AA);CES1A2-816 was divided into homozygous wild type(AA),heterozygous variant(AC),homozygous variant(CC).The end events were recorded within one year.Results The difference of platelet inhibition rate among the three types of CYP2C19* 2* 3 genotypes was statistically significant(P<0.01),among which the fast metabolism type had the highest inhibition rate and the slow metabolism type had the lowest inhibition rate. There was significant difference in platelet inhibition rate among the three types of CES1A2-816 genotypes(P<0.01),AA type had the highest inhibition rate and CC type had the lowest inhibition rate. CYP2C19* 2* 3 gene,CES1A2-816 gene and BMI > 26 kg/m^2 are independent factors of platelet inhibition rate in patients with recurrent atherosclerotic cerebral infarction.CYP2C19* 2* 3 gene and CES1A2-816 gene are independent factors of platelet inhibition rate in patients with primary atherosclerotic cerebral infarction. The carriers of CYP2C19* 2* 3 and CES1A2-816 dysfunctional alleles were independent risk factors of the main end-point events,and the age ≥60 years was also independent risk factor of the main end-point events. Conclusion The recurrence of CYP2C19* 2* 3 and CES1A2-816 alleles and the reduction of clopidogrel reactivity in patients with primary atherosclerotic cerebral infarction can increase the risk of primary end point events in patients with recurrent atherosclerotic cerebral infarction.

关 键 词：复发脑梗死 动脉粥样硬化 氯吡格雷 CYP2C19∗2∗3基因 CES1A2-816基因 

分 类 号：R743.1[医药卫生—神经病学与精神病学]