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1.
目的:系统评价对携带CYP2C19*1、*17基因型患者服用氯吡格雷的临床疗效和不良反应。方法:计算机联网检索数据库、Google等搜索引擎,收集国、内外公开发表的中文与英文文献,由2名研究人员对纳入文献提取信息,应用RevMan4.3软件进行Meta分析。结果:最终纳入7篇英文文献,共随访患者n=11759[CYP2C19*17(n=5173)、CYP2C19*1(n=6586)],Meta分析结果显示,与CYP2C19*1基因型携带组比,CYP2C19*17基因型携带组患者心血管事件发生率降低{合并统计量RR=0.82,95%CI[0.73,0.92],P<0.01},但出血事件发生率增加{RR=1.29,95%CI[1.09,1.51],P<0.01},对植入支架后再次发生血栓事件的比较无统计学意义{RR=0.88,95%CI[0.41,1.89],P>0.05}。结论:携带CYP2C19*17基因型比携带CYP2C19*1基因型患者服用氯吡格雷可明显减少心血管事件的发生,但能增加出血事件的发生。  相似文献   

2.
目的:系统评价CYP2C19*1、*2基因型心血管疾病患者对服用氯吡格雷临床疗效的影响。方法:电子检索PubMed、EBSCO、EMbase、Cochrane library、CNKI、万方中文期刊数据库及维普期刊数据库(VIP),再辅以手工检索,查找有关携带CYP2C19*1、*2基因的心血管疾病患者与氯吡格雷疗效关系的临床对照试验和观察性研究,检索时限为建库至2016年12月。由2名研究者根据纳入与排除标准独立筛选文献、质量评价及数据提取,采用RevMan 5.0软件进行Meta分析。结果:纳入5篇研究,共4544例心血管疾病患者。Meta分析结果显示:心血管疾病患者服用氯吡格雷后,CYP2C19*1和CYP2C19*2基因携带患者植入支架后血栓再形成发生率有显著差异[P=0.000 2,RR=2.46,95%CI(1.54,3.92)],其CYP2C19*2基因型携带者较CYP2C19*1型可明显增加血栓形成,但2组在心血管事件发生率上差异不显著(P>0.05)。结论:在服用氯吡格雷的心血管患者中,CYP2C19*2基因型较CYP2C19*1基因型更易发生支架后血栓,但心血管时间发生率未见明显差异,鉴于CYP2C19*2基因型携带患者发生植入支架后血栓再形成风险增加,建议在拟行PCI手术并使用氯吡格雷的患者应先测定CYP2C19*2基因型,再考虑是否应用氯吡格雷抗血小板治疗。  相似文献   

3.
目的 探讨经皮冠状动脉介入(PCI)术后患者的氯吡格雷相关基因多态性[细胞色素P4502C19(CYP2C19)、ATP结合盒亚家族B成员1(ABCB1)和对氧磷酶1(PON1)]的临床特点。方法 318例行PCI术后的患者,常规应用氯吡格雷联合阿司匹林抗栓治疗,采用荧光染色原位杂交技术检测其CYP2C19*2、CYP2C19*3、CYP2C19*17、ABCB1和PON1共5个基因位点。术后1个月用血栓弹力图筛选出氯吡格雷抵抗组和氯吡格雷正常组,比较CYP2C19相关基因发生的情况。所有患者随访6个月,记录患者的出血情况,并比较CYP2C19相关基因发生的情况。结果 318例PCI术后患者的氯吡格雷相关基因分型:CYP2C19*2基因的AA突变型10.06%, AG杂合型30.81%;CYP2C19*3基因无突变型, AG杂合型30.81%;CYP2C19*17基因无突变型, CT杂合型6.29%;ABCB1基因突变型约占9.74%, CT杂合型52.52%;PON1基因AA突变型10.06%, AG杂合型占65.41%。氯吡格雷抵抗组携带2个功能缺失(LOF)等位基因的发生率大于氯...  相似文献   

4.
目的系统评价服用氯吡格雷患者的临床疗效受P2Y12基因(T744C、G52T、C34T)多态性的影响程度,以期为其安全使用提供有效证据。方法计算机检索Web of Science、Elsevier SD、Pubmed、The Cochrane Library、Clinical Trial、CBM、CNKI,万方全文数据库及维普全文数据库,查找有关服用氯吡格雷患者P2Y12基因多态与氯吡格雷疗效相关的观察性临床试验,检索时限均从建库截至2014年8月20日。对符合条件的研究,由两位研究者按照纳入和排除标准,独立筛选文献、提取资料、评价质量,并交叉核对后,采用Rev Man 5.3软件和Stata12.0软件进行Meta分析。结果共纳入13篇文献,包含13个观察性临床研究(n=2 787)。Meta分析结果显示:P2Y12基因突变有增加亚洲人群氯吡格雷抵抗发生率[相对危险度(RR)=1.44,95%CI(1.11,1.88),P=0.007],其中P2Y12基因位点G52T和C34T增加氯吡格雷抵抗[分别为RR=1.28,95%CI(1.06,1.56),P=0.01和RR=2.70,95%CI(1.37,5.29),P=0.004],同时增加心血管不良事件[分别是RR=1.99,95%CI(1.63,2.44),P<0.000 01和RR=1.31,95%CI(1.07,1.62),P=0.01],而T744C对发生氯吡格雷抵抗和不良心血管事件均无影响[分别为RR=1.02,95%CI(0.64,1.61),P=0.94和RR=0.74,95%CI(0.36,1.50),P=0.40]。结论血小板P2Y12受体基因突变可能增加氯吡格雷抵抗发生率,其中G52T和C34T在增加氯吡格雷抵抗和心血管不良事件起着重要作用,而T744C对其均无影响。由于本次研究存在一些不足,血小板P2Y12受体基因多态性对服用氯吡格雷患者的临床疗效影响还待进一步研究证实。  相似文献   

5.
邸晓辉  边佳明  徐娟  张梅 《中国药房》2014,(20):1872-1874
目的:探讨影响我国北方汉族冠心病人群氯吡格雷抵抗的相关影响因素。方法:选择425例首次行经皮冠状动脉介入术的患者,根据血小板聚集率结果将患者分为氯吡格雷抵抗(CRG)组和氯吡格雷敏感(CSG)组。检测其基因型,分析其CYP2C19*2等位基因携带状态,并分析血小板聚集率等实验室指标和冠心病易感指标等与其是否发生氯吡格雷抵抗的相关性。结果:CYP2C19基因G681A突变携带者(GA、AA)在CRG组与CSG组的分布率分别为64.4%和33.1%,携带突变基因与否在两组间的分布比较差异具有统计学意义(P<0.000 1),而其他非遗传性指标在两组间比较差异无统计学意义(P>0.05)。结论:CYP2C19*2等位基因的携带与氯吡格雷抵抗有显著的相关性,G681A突变基因的携带是导致氯吡格雷抵抗的危险因素,其他非遗传因素与氯吡格雷抵抗的关联不大。  相似文献   

6.
目的:探讨新疆维吾尔族急性冠脉综合征(ACS)患者CYP2C19基因多态性与氯吡格雷抗血小板反应性的相关性。方法:选取2018年1月-2019年1月新疆喀什地区第二人民医院心血管内科收治的维吾尔族ACS患者90例,予阿司匹林+氯吡格雷双联抗血小板治疗且出院后持续用药1年。检测患者血小板聚集抑制率(DPAI),评价其对氯吡格雷的反应性。采用聚合酶链式反应(PCR)-荧光探针法检测其CYP2C19*2、*3基因分型,采用PCR-直接测序法检测其CYP2C19*17基因分型。采用多因素Logistic回归分析探讨基因和非基因因素与患者DPAI的相关性。结果:90例患者中,氯吡格雷抵抗(CR)的患者有10例,非CR患者有80例。CYP2C19*2 G/G、G/A、A/A型患者分别有58、28、4例,CYP2C19*3 G/G、G/A型患者分别有88、2例,CYP2C19*17 C/C、C/T型患者分别有64、26例,各基因型频率均符合Hardy-Weinberg平衡(P>0.05)。治疗后,CYP2C19*2 G/A、A/A型患者DAPI均较G/G型患者显著降低,且A/A型患者DAPI显...  相似文献   

7.
目的 系统评价替格瑞洛和氯吡格雷治疗携带CYP2C19功能缺失等位基因的轻度缺血性卒中或短暂性脑缺血发作患者的有效性和安全性。方法 系统检索PubMed、Embase、the Cochrane Library、CNKI、万方数据库等数据库,检索时限均为从建库至2022年6月。由2名研究者独立筛选文献、提取资料并评价纳入研究的方法学质量,使用RevMan 5.3软件进行Meta分析。结果 共纳入2篇研究,7087例患者。与氯吡格雷比较,替格瑞洛降低携带CYP2C19 LOF等位基因的轻度缺血性卒中或短暂性脑缺血发作患者卒中[RR=0.78,95%CI(0.66-0.93),I2=0%,P=0.007]和血管事件发生率[RR=0.78,95%CI(0.66-0.91),I2=0%,P=0.002]。替格瑞洛-阿司匹林组任何出血[HR=2.18,95%CI(1.66-2.85)]和小出血[HR=2.41,95%CI(1.81-3.20)]发生率高于氯吡格雷-阿司匹林组,且替格瑞洛-阿司匹林组呼吸困难(1.2% vs 0.2%,P<0.001)和心律失常(1.7% vs 0.8%,P=0.001)发生率比氯吡格雷-阿司匹林组更常见;两组严重出血发生率差异无统计学意义。结论 与氯吡格雷比较,替格瑞洛降低携带CYP2C19 LOF等位基因的轻度缺血性卒中或TIA患者卒中和血管事件发生率,且不增加严重出血风险;但替格瑞洛组小出血、呼吸困难和心律失常发生率高。  相似文献   

8.
目的观察药物代谢酶系统中CYP2C19基因多态性及患者主要临床资料与服用氯吡格雷前后血小板聚集率变化(氯吡格雷药物抵抗)的相关性。方法入选拟行冠脉造影检查或支架植入治疗患者35例,根据围手术期应用氯吡格雷前后血小板聚集率变化,将患者分为氯吡格雷抵抗组和非抵抗组。检测CYP2C19基因型,并记录患者年龄、性别、烟酒史、高血压、糖尿病等主要临床资料,分析基因水平及临床水平各因素对血小板聚集及氯吡格雷药物抵抗的影响。结果检测出氯吡格雷抵抗的患者15例,CYP2C19慢代谢基因型患者4例,Logistic回归分析显示,CYP2C19基因型是氯吡格雷抵抗的危险因素(OR=1.236,95%CI:0.273~5.599,P=0.049)。结论 CYP2C19基因型在基因水平与氯吡格雷抵抗相关,临床水平资料未见明显相关性。  相似文献   

9.
吴晓峰 《安徽医药》2019,23(4):679-682
目的 探究CYP2C19*2和CYP2C19*17基因多态性与冠状动脉介入治疗后病人氯吡格雷反应性的关系。方法 青海省心脑血管病专科医院于2014年3月至2017年3月期间招募了347例经皮冠状动脉介入的支架植入病人。采集经氯吡格雷(75 mg/d)治疗至少7 d的病人血液样品,用VerifyNow P2Y12测定法测量血小板活性(PRU)和(%)抑制性。应用聚合酶链式反应检测CYP2C19*2(rs4244285)和CYP2C19*17(rs12248560)基因多态性,比较氯吡格雷应答组和无应答组病人CYP2C19*2(rs4244285)和CYP2C19*17(rs12248560)基因型的分布频率差异以及等位基因频率差异。结果 分组时,PRU>208的病人对氯吡格雷治疗无反应;104例(30%)病人为无应答者,243例(70%)病人为应答者。243例氯吡格雷应答组和104例无应答组CYP2C19*2(rs4244285)基因型分布频率野生型GG为80.7%/54.8%,杂合型GA为17.3%/38.5%,突变型AA为2.1%/6.7%,两组比较χ2=7.04,P<0.001;等位基因频率野生型G为89.3%/74.0%,突变型A为10.7%/26.0%,两组比较χ2=5.25,P<0.001。CYP2C19*17(rs12248560)基因型分布频率野生型CC为67.9%/75.0%,杂合型CT为30.5%/23.1%,突变型TT为1.6%/1.9%,两组比较χ2=0.81,P=0.388;等位基因频率野生型C为83.1%/84.1%,突变型T为16.9%/13.1%,两组比较χ2=0.68,P=0.416。结论 CYP2C19*2多态性与氯吡格雷治疗无反应相关,CYP2C19*17多态性增强了氯吡格雷的抗血小板活性。根据这两种多态性的单倍型,氯吡格雷治疗的病人可以被保护或不受支架血栓形成和缺血事件的威胁。  相似文献   

10.
目的探讨细胞色素P450酶2C19基因(CYP2C19)681G/A多态性对氯吡格雷治疗冠状动脉粥样硬化性心脏病(CAHD)的影响。方法选取佛山市南海区第二人民医院心内科CADH患者274例,其中130例口服氯吡格雷,选取佛山市111例调查的自然人群为对照组,口服氯吡格雷患者中52例进行了择期经皮冠状动脉介入术(PCI)治疗,比较氯吡格雷治疗后患者各基因型与实验室氯吡格雷抵抗之间的关系,并分别比较不同基因型组间血小板聚集率、实验室氯吡格雷抵抗和不良心血管事件的再发生情况。结果氯吡格雷治疗后CYP2C19681AA型平均血小板聚集率降低幅度最小,GA型次之,GG型最高;PCI患者CYP2C19681A等位基因携带者组不良心血管事件再发率高、平均血小板聚集率降低幅度小、实验室氯吡格雷抵抗发生率高。结论 CYP2C19681G/A突变是CAHD患者口服氯吡格雷治疗疗效及预后欠佳的主要影响因素,它减弱了氯吡格雷对血小板的抑制作用。  相似文献   

11.
AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians. RESULTS: Both CYP2C19 loss-of-function alleles (*2 or *3) were associated with higher platelet reactivity while the CYP2C19 gain-of-function allele (*17) had lower platelet reactivity. For PON1, the median PRI was not significantly different between the QQ, QR and RR groups. The allele frequencies of CYP2C19*2, CYP2C19*3 and CYP2C19*17 were 0.280, 0.065 and 0.010 (rare) for Chinese, 0.310, 0.050 and 0.025 for Malays, and 0.375, 0.010 (rare) and 0.165 for Indians, respectively. CONCLUSION: Our data suggest that genotyping studies to investigate clopidogrel response should include CYP2C19*2 and *3 but not *17 polymorphisms in Chinese, and CYP2C19*2 and *17 polymorphisms but not *3 in Indians. All three polymorphisms should preferably be genotyped in Malays.  相似文献   

12.

Background

The antiplatelet activity of clopidogrel is variable among patients suffering from ischemic heart disease. Variation in the cytochrome P450 2C19 (CYP2C19) gene coding for the CYP2C19 enzyme is one of the major determinants of this variable response to clopidogrel. The activity of the CYP2C19 enzyme, which plays a role in the conversion of the prodrug clopidogrel to its active metabolite, is genetically influenced by polymorphisms in its gene. The aim of our study was to evaluate the association of CYP2C19 polymorphisms and the antiplatelet effect of clopidogrel in the South Indian Tamilian population.

Materials and methods

Genotyping and platelet aggregation results of 149 ischemic heart disease patients on clopidogrel maintenance therapy (75 mg daily dose) were analyzed in this study. CYP2C19 polymorphisms were genotyped by the PCR-restriction fragment length polymorphism method. We measured residual platelet activities in these patients on clopidogrel therapy in terms of impedance (expressed as ohms). The study subjects were divided into two metabolizer phenotype groups [group 1: poor/intermediate metabolizers (PM/IM); group 2: extensive/ultra-rapid metabolizers (EM/URM)] based on CYP2C19 genotype, and the residual platelet activities were compared. Higher values of impedance denote increased residual platelet activity.

Results

Poor/intermediate metabolizers had significantly higher impedance values than EM/URM [(median; range) 4.0; 0–13 vs. 2.0; 0–11, respectively; p?=?0.04]. These higher impedance values denote higher residual platelet activities among the carriers of loss-of-function alleles (CYP2C19*2,*3) than among non-carriers. However, residual platelet activities were lower among the carriers of the gain-of-function allele (CYP2C19*17) than among non-carriers, although this difference was not significant.

Conclusion

Patients with CYP2C19 (*2 or *3) genetic polymorphisms had higher residual platelet activities and were associated with a reduced antiplatelet response to clopidogrel. As the South Indian Tamilian population is characterized with higher frequencies of these genetic polymorphisms, our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy.  相似文献   

13.
目的:研究PCI术后患者PON1-126C>G基因多态性对氯吡格雷抗血小板治疗后出血事件的影响。方法:研究对象选自2014年6月至2015年9月,在某院心内科住院行PCI术的患者,所有患者均接受标准双联抗血小板治疗。收集全血,提取DNA,采用Sequenom MassARRAY 基因分型技术进行PON1-126C>G、CYP2C19*17基因型分析;采用HPLC-UV法测定羧酸氯吡格雷代谢物(CLPM)血药浓度;采用PL-11血小板分析仪检测血小板聚集功能;随访患者PCI术后12个月内的出血事件。结果:共纳入384例患者,依据随访结果,分为出血组与非出血组,PON1-126G突变型即CG+GG基因型分布频率在2组之间的差异具有显著性(28.57% vs. 13.47%,χ2=4.712,P=0.046);CYP2C19*17突变型即CT基因型分布频率在两组之间的差异也具有显著性(10.71% vs. 2.30%,χ2=6.462,P=0.041)。结论:PON1 -126 CG+GG基因型与PCI术后12个月内氯吡格雷所致出血事件发生显著相关,该基因型检测可有效预测出具有出血风险的高危患者,从而调整氯吡格雷给药方案,改善预后。  相似文献   

14.
目的:探讨颅内动脉瘤(IAs)患者支架辅助栓塞术(SAC)术后氯吡格雷治疗时血小板高反应性(HTPR)的风险因素,并构建Logistic回归模型,分析该模型对IAs患者SAC术后氯吡格雷治疗时HTPR风险的预测.方法:入组160例SAC术后患者,给予阿司匹林和氯吡格雷抗血小板治疗,连续服用5 d,晨起抽取静脉血,检测血...  相似文献   

15.

Purpose

Chinese people are more frequent carriers of cytochrome P450 2C19 (CYP2C19) loss-of-function alleles than Caucasians. The effect of the ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase 1 (PON1) variants on platelet reactivity and clinical outcomes of clopidogrel treatment has not yet been reported in Chinese patients after percutaneous coronary intervention. The aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1 variants on clopidogrel pharmacodynamics and clinical outcomes in these patients.

Methods

Six hundred and seventy patients after percutaneous coronary intervention were enrolled in a single-center registry. The antiplatelet effect of clopidogrel was assessed by thromboelastography, and the CYP2C19, ABCB1, and PON1 genotypes were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.

Results

The frequency of the CYP2C19 loss-of-function alleles was relatively high (57.3 %). The risk of a low response to clopidogrel and composite ischemic events increased with the number of CYP2C19 loss-of-function alleles. However, there were not significant differences in clopidogrel pharmacodynamics and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not significantly different across the CYP2C19, ABCB1, and PON1 genotype groups.

Conclusions

The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients.  相似文献   

16.
徐林  金立军 《安徽医药》2017,21(4):687-691
目的 探讨高危急性冠脉综合征(ACS)病人经皮冠状动脉支架植入术 (PCI)术后对P2Y12受体拮抗剂抑制血小板聚集的反应性及影响因素,同时在此基础上探讨对病人预后的影响.方法 86例ACS行PCI术病人,分为氯吡格雷抵抗(CR)组24例,无氯吡格雷抵抗(NCR)组62例.运用焦磷酸测序技术,检测其CYP2C19*2,*3单核苷酸多态性及二磷酸腺苷(ADP)诱导的血小板聚集率,分析病人CR与基因型的关系.经Logistic回归分析CR的影响因素,并对病人进行1年的心脏不良事件(MACE)、卒中、呼吸困难、出血事件的随访.结果 单因素及Logistic回归分析表明,野生基因型(OR=0.15,P=0.011,95%CI=0.04~0.67)是CR的保护因素;而高血压病史(P=0.021,OR=8.136,95%CI=1.48~44.80)、空腹血糖值(P=0.012,OR=1.51,95%CI=1.10~2.06)、基础血小板聚集率(P=0.023,OR=1.06,95%CI=0.01~1.11)等3个因素是CR的危险影响因素;此外,术后1年随访,总MACE发生率CR组为29.2%,明显高于NCR的9.7%.结论 CYP2C19基因型与CR引发的心血管事件有重要关联.CYP2C19野生型基因是高危ACS病人发生CR的保护因素;高血压病史、高空腹血糖值、血小板高反应性为CR的危险因素,CR组病人PCI术后MACE事件显著增高.CYP2C19*2,*3是CR发生的独立预测因子,CR作为独立危险因素,预示着心血管事件发生的危险增加.  相似文献   

17.

BackgroundCYP2C19 loss-of-function polymorphic alleles (*2 and *3) have been documented to impair clopidogrel metabolism, and represent a risk factor for major adverse cardiac events. CYP2C19 polymorphism exhibits marked ethnic heterogeneity. Objective To determine the prevalence of CYP2C19 *2 and *3 alleles in a cohort of Palestinian patients managed with percutaneous coronary intervention and dual antiplatelet therapy, and to determine their role in causing major adverse cardiac events. Setting The blood samples were collected at the European Gaza Hospital, and the molecular techniques performed at the molecular genetics laboratory of the Islamic university of Gaza. Method The frequency of CYP2C19 *2 and *3 alleles was determined in 110 patients managed with percutaneous coronary intervention and clopidogrel. Genotyping was performed by PCR–RFLP. Personal and clinical data was obtained from patient record and 6-month follow-up for major adverse cardiac events. Main outcome measureCYP2C19 genotype, personal and clinical data and incidence of major adverse cardiac events. Results The frequency of CYP2C19 *1, *2 and *3 alleles was 82.3%, 15.5% and 2.3% respectively. Genotyping analysis showed that, 67.3% were homozygotes for CYP2C19 *1, 27.3% were *1/*2, 2.7% with *1/*3 genotype, 1.8% were *2/*3 and 0.9% were *2/*2. These frequencies were consistent with those of Caucasian populations. According to this study the poor metabolizers phenotype frequency was 2.7%, which is in the same range reported in Caucasians (2–5%) and lower than Oriental populations 13–23%. A strong significant relation was found between major adverse cardiac events and carrying the variant allele CYP2C19 *2 (P?=?0.001). On the other hand, there was no significant relation between major adverse cardiac events and carrying the variant allele CYP2C19 *3 (P?=?0.324). Conclusion The CYP2C19 *2 allele is relatively common in our population, and its associated reduced metabolic activity deserves attention as it leads to an increased incidence of major adverse cardiac events in the follow-up of patients receiving clopidogrel.

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