P2Y12受体基因多态性与冠心病人群氯吡格雷抵抗相关性的Meta分析
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摘要
目的:通过Meta分析探讨冠心病人群中P2Y12受体(P2RY12)基因多态性与氯吡格雷抵抗的相关性。方法:检索PubMed、Cochrane、Medline、中国知网和万方数据库,检索时间截至2018年3月,根据入选标准筛选文献。所纳入研究的血小板功能由光透射凝集试验(LTA)检测。根据是否存在氯吡格雷抵抗,将患者分为氯吡格雷抵抗组和未抵抗组。通过4种遗传模型分析所有纳入的P2RY12基因位点。此外,根据地理区域进行亚组分析。所有分析程序均由Review Manager 5.2软件执行。结果:纳入6项研究,共2 236例受试者。P2RY12基因T744C多态性的显性模型与氯吡格雷抵抗显著相关(OR:0.73,95%CI:0.59～0.90,P<0.01)。在亚组分析中,T744C位点的显性模型与欧美地区冠心病人群的氯吡格雷抵抗呈负相关(OR:0.34,95%CI:0.23～0.49,P<0.01)。C34T位点遗传模型与氯吡格雷抵抗之间无相关性。结论:冠心病人群中P2RY12基因的T744C位点CC基因型是氯吡格雷抵抗发生的保护因素,在欧美地区尤其显著。C34T位点与氯吡格雷抵抗之间没有相关性。P2RY12基因的T744C位点可作为PCI术后对氯吡格雷用药指导的检测位点。
Objective:To address the association between P2Y12 receptor(P2RY12)gene polymorphisms and clopidogrel resistance in coronary heart disease(CHD)by a Meta-analysis.Method:The relevant studies were identified by searching the database of PubMed,Cochrane,Medline,Chinese National Knowledge Infrastructure(CNKI)and Wanfang.Articles up to March 2018 were included.All the platelet function of included studies was detected by light transmission aggregometry(LTA)method.According to whether there was the presence of clopidogrel resistance,all patients were divided into two groups.Then,all included polymorphisms of P2RY12 gene were examined by four kinds of genetic models.Also,based on geographic region,a subgroup analysis was conducted in this study.All analysis procedures of this Meta-analysis were performed by the Review Manager 5.2 software.Result:Six studies with a total of 2236 subjects were included.The dominant model of T744C polymorphisms in P2RY12 gene was associated with clopidogrel resistance(OR:0.73,95%CI:0.59-0.90,P<0.01).In subgroup analysis,the results also noted a association between the dominant model of T744C polymorphisms and clopidogrel resistance in European and America region(OR:0.34,95%CI:0.23-0.49,P<0.01).However,there was no evidence suggested a association between C34T genetic models and clopidogrel resistance.Conclusion:The CC genotype of T744C polymorphism in P2RY12 gene might be a protective factor of clopidogrel resistance in CHD,especially in European and America region.However,there is no relationship between C34T polymorphisms and clopidogrel resistance in CHD.The T744C polymorphism of P2RY12 gene would be regarded as guidance for clopidogrel therapy in patients with CHD.
Objective:To address the association between P2Y12 receptor(P2RY12)gene polymorphisms and clopidogrel resistance in coronary heart disease(CHD)by a Meta-analysis.Method:The relevant studies were identified by searching the database of PubMed,Cochrane,Medline,Chinese National Knowledge Infrastructure(CNKI)and Wanfang.Articles up to March 2018 were included.All the platelet function of included studies was detected by light transmission aggregometry(LTA)method.According to whether there was the presence of clopidogrel resistance,all patients were divided into two groups.Then,all included polymorphisms of P2RY12 gene were examined by four kinds of genetic models.Also,based on geographic region,a subgroup analysis was conducted in this study.All analysis procedures of this Meta-analysis were performed by the Review Manager 5.2 software.Result:Six studies with a total of 2236 subjects were included.The dominant model of T744C polymorphisms in P2RY12 gene was associated with clopidogrel resistance(OR:0.73,95%CI:0.59-0.90,P<0.01).In subgroup analysis,the results also noted a association between the dominant model of T744C polymorphisms and clopidogrel resistance in European and America region(OR:0.34,95%CI:0.23-0.49,P<0.01).However,there was no evidence suggested a association between C34T genetic models and clopidogrel resistance.Conclusion:The CC genotype of T744C polymorphism in P2RY12 gene might be a protective factor of clopidogrel resistance in CHD,especially in European and America region.However,there is no relationship between C34T polymorphisms and clopidogrel resistance in CHD.The T744C polymorphism of P2RY12 gene would be regarded as guidance for clopidogrel therapy in patients with CHD.
引文
[1]李为民,臧雁翔.冠心病双联抗血小板治疗优化策略的思考[J].临床心血管病杂志,2018,34(10):943-945.
[2]郭琳娟,洪葵.氯吡格雷抵抗的影响因素[J].临床心血管病杂志,2015,31(11):1150-1154.
[3]Cattaneo M.P2Y12receptors:structure and function[J].J Thromb Haemost,2015,13Suppl 1:S10-16.
[4]Zhang Y,Zhang S,Ding Z.Role of P2Y12receptor in thrombosis[J].Adv Exp Med Biol,2017,906:307-324.
[5]Roule V,Ardouin P,Repesse Y,et al.Point of care tests VerifyNow P2Y12and INNOVANCE PFA P2Ycompared to light transmittance aggregometry after fibrinolysis[J].Clin Appl Thromb Hemost,2018,24(7):1109-1116.
[6]Galic E,Vrbanic L,Kapitanovic S,et al.P2RY12gene polymorphisms and effect of clopidogrel on platelet aggregation[J].Coll Antropol,2013,37(2):491-498.
[7]Yang HH,Chen Y,Gao CY.Associations of P2Y12Rgene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel[J].Cardiovasc Ther,2016,34(6):460-467.
[8]Yang HH,Chen Y,Gao CY.Associations of P2Y12Rgene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel[J].Cardiovasc Ther,2016,34(6):460-467.
[9]Li M,Wang H,Xuan L,et al.Associations between P2RY12gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCIin patients with acute coronary syndrome[J].Medicine,2017,96(14):e6553.
[10]Cuisset T,Frere C,Quilici J,et al.Role of the T744Cpolymorphism of the P2Y12gene on platelet response to a 600-mg loading dose of clopidogrel in 597patients with non-ST-segment elevation acute coronary syndrome[J].Thromb Res,2007,120(6):893-899.
[11]Lev EI,Patel RT,Guthikonda S,et al.Genetic polymorphisms of the platelet receptors P2Y(12),P2Y(1)and GP IIIa and response to aspirin and clopidogrel[J].Thromb Res,2007,119(3):355-360.
[12]Liang ZY,Han YL,Zhang XL,et al.The impact of gene polymorphism and high on-treatment platelet reactivity on clinical follow-up:outcomes in patients with acute coronary syndrome after drug-eluting stent implantation[J].EuroIntervention,2013,9(3):316-327.
[13]Calderon-Cruz B,Rodriguez-Galvan K,Manzo-Francisco LA,et al.C3435T polymorphism of the ABCB1gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention[J].Thromb Res,2015,136(5):894-898.
[14]Zhao K,Yang M,Lu Y,et al.P2Y12polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel:a meta-analysis[J].Drug Res(Stuttg),2018,doi:10.1055/a-0622-8110.
[15]Cui G,Zhang S,Zou J,et al.P2Y12receptor gene polymorphism and the risk of resistance to clopidogrel:Ameta-analysis and review of the literature[J].Adv Clin Exp Med,2017,26(2):343-349.
[2]郭琳娟,洪葵.氯吡格雷抵抗的影响因素[J].临床心血管病杂志,2015,31(11):1150-1154.
[3]Cattaneo M.P2Y12receptors:structure and function[J].J Thromb Haemost,2015,13Suppl 1:S10-16.
[4]Zhang Y,Zhang S,Ding Z.Role of P2Y12receptor in thrombosis[J].Adv Exp Med Biol,2017,906:307-324.
[5]Roule V,Ardouin P,Repesse Y,et al.Point of care tests VerifyNow P2Y12and INNOVANCE PFA P2Ycompared to light transmittance aggregometry after fibrinolysis[J].Clin Appl Thromb Hemost,2018,24(7):1109-1116.
[6]Galic E,Vrbanic L,Kapitanovic S,et al.P2RY12gene polymorphisms and effect of clopidogrel on platelet aggregation[J].Coll Antropol,2013,37(2):491-498.
[7]Yang HH,Chen Y,Gao CY.Associations of P2Y12Rgene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel[J].Cardiovasc Ther,2016,34(6):460-467.
[8]Yang HH,Chen Y,Gao CY.Associations of P2Y12Rgene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel[J].Cardiovasc Ther,2016,34(6):460-467.
[9]Li M,Wang H,Xuan L,et al.Associations between P2RY12gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCIin patients with acute coronary syndrome[J].Medicine,2017,96(14):e6553.
[10]Cuisset T,Frere C,Quilici J,et al.Role of the T744Cpolymorphism of the P2Y12gene on platelet response to a 600-mg loading dose of clopidogrel in 597patients with non-ST-segment elevation acute coronary syndrome[J].Thromb Res,2007,120(6):893-899.
[11]Lev EI,Patel RT,Guthikonda S,et al.Genetic polymorphisms of the platelet receptors P2Y(12),P2Y(1)and GP IIIa and response to aspirin and clopidogrel[J].Thromb Res,2007,119(3):355-360.
[12]Liang ZY,Han YL,Zhang XL,et al.The impact of gene polymorphism and high on-treatment platelet reactivity on clinical follow-up:outcomes in patients with acute coronary syndrome after drug-eluting stent implantation[J].EuroIntervention,2013,9(3):316-327.
[13]Calderon-Cruz B,Rodriguez-Galvan K,Manzo-Francisco LA,et al.C3435T polymorphism of the ABCB1gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention[J].Thromb Res,2015,136(5):894-898.
[14]Zhao K,Yang M,Lu Y,et al.P2Y12polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel:a meta-analysis[J].Drug Res(Stuttg),2018,doi:10.1055/a-0622-8110.
[15]Cui G,Zhang S,Zou J,et al.P2Y12receptor gene polymorphism and the risk of resistance to clopidogrel:Ameta-analysis and review of the literature[J].Adv Clin Exp Med,2017,26(2):343-349.
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