CAJ | 학술논문

目的探讨细胞色素P450酶2C19(CYP2C19)基因多态性与缺血性脑血管病患者介入术后长期服用氯吡格雷临床预后的相关性.方法入选南京卒中注册系统中2009年4月至2010年12月行脑血管支架植入术并长期服用氯吡格雷的缺血性卒中患者194例.采用多重高温连接酶检测反应技术对人选病例的CYP2C19*2和CYP2C19 * 3位点进行分型,并对这些患者进行随访.主要终点事件包括缺血性脑血管事件和死亡；次要终点事件包括出血性血管事件和其他血管事件.结果平均随访(19.4±9.9)个月,主要终点事件发生率为16.5％ (32/194).CYP2C19*2基因位点分型结果显示,194例患者中,CYP2C19*1*1型患者87例(44.8％),CYP2C19*1 * 2型患者88例(45.4％),CYP2C19 * 2*2型患者19例(9.8％).携带CYP2C19 * 2基因的患者随访期间主要终点事件的发生率明显高于非携带者[24/107(22.4％)与8/87(9.2％),HR =2.74,95％ CI 1.23 ～6.10,p=0.01].CYP2C19*3基因位点分型结果显示,CYP2C19 * 1 * 1基因型患者181例(93.3％),CYP2C19 * 1 * 3基因型患者13例(6.7％).CYP2C19 * 1*1和CYP2C19*1*3的两组患者之间主要终点事件发生率的差异无统计学意义.将年龄、性别、体重指数、高血压、糖尿病等危险因素纳入多因素COX回归模型分析显示,CYP2C19*2是主要终点事件的发生独立危险因素(HR=2.89,95％ Cl 1.10 ～7.60,P=0.03).结论 CYP2C19*2基因位点的多态性可能是影响脑血管支架术后服用氯吡格雷的患者临床预后的重要影响因素.
목적 탐토세포색소P450매2C19(CYP2C19)기인다태성여결혈성뇌혈관병환자개입술후장기복용록필격뢰림상예후적상관성.방법 입선남경졸중주책계통중2009년4월지2010년12월행뇌혈관지가식입술병장기복용록필격뢰적결혈성졸중환자194례.채용다중고온련접매검측반응기술대인선병례적CYP2C19*2화CYP2C19 * 3위점진행분형,병대저사환자진행수방.주요종점사건포괄결혈성뇌혈관사건화사망；차요종점사건포괄출혈성혈관사건화기타혈관사건.결과 평균수방(19.4±9.9)개월,주요종점사건발생솔위16.5％ (32/194).CYP2C19*2기인위점분형결과현시,194례환자중,CYP2C19*1*1형환자87례(44.8％),CYP2C19*1 * 2형환자88례(45.4％),CYP2C19 * 2*2형환자19례(9.8％).휴대CYP2C19 * 2기인적환자수방기간주요종점사건적발생솔명현고우비휴대자[24/107(22.4％)여8/87(9.2％),HR =2.74,95％ CI 1.23 ～6.10,p=0.01].CYP2C19*3기인위점분형결과현시,CYP2C19 * 1 * 1기인형환자181례(93.3％),CYP2C19 * 1 * 3기인형환자13례(6.7％).CYP2C19 * 1*1화CYP2C19*1*3적량조환자지간주요종점사건발생솔적차이무통계학의의.장년령、성별、체중지수、고혈압、당뇨병등위험인소납입다인소COX회귀모형분석현시,CYP2C19*2시주요종점사건적발생독립위험인소(HR=2.89,95％ Cl 1.10 ～7.60,P=0.03).결론 CYP2C19*2기인위점적다태성가능시영향뇌혈관지가술후복용록필격뢰적환자림상예후적중요영향인소.
Objective To evaluate the impact of cytochrome P450 (CYP) 2C19 gene polymorphisms on clinical outcome in clopidogrel-treated patients who underwent cerebrovascular stenting placement.Methods One hundred and ninty-four patients who underwent cerebrovascular stent placement and with long-term treatment of clopidogrel (75 mg/d) between April 2009 and December 2010 were enrolled,CYP2C19 genotype was detected by improved multiple ligase detection reaction.The primary clinical endpoints were ischemic stroke and death after stent implantation; the key secondary endpoints were hemorrhagic stroke and other vascular events.Results The average followed-up was (19.4 ± 9.9) months.The overall incidence of primary endpoints was 16.5％.Of the 194 patients,87 (44.8％) were wild-type homozygous,88 (45.4％) were heterozygotes,and 19 (9.8％) were homozygous.The cumulative incidence of adverse outcomes was significant higher in CYP2C19 * 2 carrier than that in noncarriers (22.4％ (24/107) vs9.2％(8/87),HR=2.74,95％ Cl1.23-6.10,P=0.01).Of the 194 patients,13 (6.7％) were heterozygotes,and 181 (93.3％) were wild-type homozygous.CYP2C19*3 polymorphism had no significanl impact on the outcomes in this cohort of patients.No relationship between gene and the secondary endpoints were detected.After multivariable analysis,the CYP2C19* 2 was an independent predictor of clinical outcomes of cerebrovascular stent placement (HR =2.89,95％ Cl 1.10-7.60,P =0.03).Conclusions CYP2C19 *2 is an independent determinant of adverse events after cerebrovascular stent placement treated with clopidogrel.While CYP2C19* 3 is not associated with the clinical prognosis in patients with cerehrovascular stent placement.