氯吡格雷相关基因多态性与缺血性脑卒中早期神经功能恶化的相关性研究  

Variants in clopidogrel-relevant genes and early neurological deterioration in ischemic stroke patients receiving clopidogrel

作　　者：卿婷 易兴阳 王淳[2] 曾涛[2] 罗华[1] 李作孝 林静 周强 QING Ting;YI Xingyang;WANG Chun;ZENG Tao;LUO Hua;LI Zuoxiao;LIN Jing;ZHOU Qiang(Department of Neurology,the Affiliated Hospital of Southwest Medical University,Luzhou,Sichuan 646000,P.R.China;Department of Neurology,People’s Hospital of Deyang City,Deyang,Sichuan 618000,P.R.China;Department of Neurology,the Third Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325200,P.R.China)

机构地区：[1]西南医科大学附属医院神经内科,四川泸州646000 [2]德阳市人民医院神经内科,四川德阳618000 [3]温州医科大学附属第三医院神经内科,浙江温州325200

出　　处：《华西医学》2022年第6期830-837,共8页West China Medical Journal

基　　金：四川省卫生和计划生育委员会科研课题(140025);德阳市2014年度重点科学技术研究项目(2014SZ035)。

摘　　要：目的评估16个氯吡格雷相关基因位点多态性与接受氯吡格雷治疗的急性缺血性卒中(acute ischemic stroke,AIS)患者发生早期神经功能恶化(early neurological deterioration,END)的相关性。方法连续纳入2014年6月—2015年1月入住3家医院神经内科的AIS患者。采用质谱法检测16个氯吡格雷相关基因位点的多态性,多因子降维法(generalized multifactor dimensionality reduction,GMDR)分析基因-基因之间的交互作用。原发终点为入院后10 d内END。结果共纳入AIS患者375例。95例(25.33%)发病后10 d内发生END。单因素分析16个基因多态性,仅CYP2C19*2 rs4244285 AG+AA与END相关(P<0.001)。但GMDR示,CYP2C19*2 rs4244285、P2Y12 rs16863323和GPⅢa rs2317676这3个基因位点存在交互作用(P=0.019)。Cox分析显示,这3个基因位点高风险交互基因型是END发生的独立预测因素[风险比=2.184,95%置信区间(1.472,3.238),P=0.004]。结论AIS后END发生率高,CYP2C19*2 rs4244285、P2Y12 rs16863323及GPⅢa rs2317676这3个基因位点的交互作用可能增加END发生的风险,对携带这3个基因位点高风险交互基因型患者可能应及时调整氯吡格雷的治疗策略。Objective To evaluate the associations of 16 variants in clopidogrel-relevant genes with early neurological deterioration(END)in acute ischemic stroke(AIS)patients receiving clopidogrel treatment.Methods AIS patients admitted to the Department of Neurology of three hospitals between June 2014 and January 2015 were included.The 16 variants in clopidogrel-relevant genes were examined using mass spectrometry.Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction(GMDR)methods.The primary outcome was END within the 10 days of admission.Results A total of 375 patients with AIS were included.Among the 375 patients,95(25.33%)patients developed END within the first 10 days of admission.Among the 16 variants,only CYP2C19*2 rs4244285AG+AA was associated with END using single-locus analytical approach(P<0.001).GMDR analysis revealed that there was a synergistic effect of gene-gene interactions among CYP2C19*2 rs4244285,P2Y12 rs16863323,and GPⅢa rs2317676on risk for END(P=0.019).Cox regression analysis showed that the high-risk interactive genotype was independent predictor for END[hazard ratio=2.184,95%confidence interval(1.472,3.238),P=0.004].Conclusions END is very common in patients with AIS.Interactions among CYP2C19*2 rs4244285,P2Y12 rs16863323,and GPⅢa rs2317676 may confer a higher risk for END.It may be very important to modify clopidogrel therapy for the patients carrying the highrisk interactive genotype.

关 键 词：缺血性脑卒中 早期神经功能恶化 氯吡格雷 基因多态性 多因子降维法 

分 类 号：R743.3[医药卫生—神经病学与精神病学]