文章摘要
吴晓峰.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联分析[J].安徽医药,2019,23(4):679-682.
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联分析
Correlation analysis of CYP2C19*2 and CYP2C19*17 polymorphisms with patients clopidogrel responsiveness after percutaneous coronary intervention
投稿时间:2019-03-03  
DOI:
中文关键词: 细胞色素P450酶系统  多态现象,遗传  血管成形术,气囊,冠状动脉  氯吡格雷
英文关键词: Cytochrome P-450 enzyme system  Polymorphism,genetic  Angioplasty,balloon,coronary  Clopidogrel
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作者单位
吴晓峰 青海省心脑血管病专科医院心内科,青海 西宁 810000 
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中文摘要:
      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。
英文摘要:
      Objective To investigate the correlation of the CYP2C19*2 and CYP2C19*17 polymorphisms with patients clopidogrel responsiveness after percutaneous coronary intervention.Methods A total of 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation in the Qinghai Cardiovascular Hospital from March 2014 to March 2017 were included in our study.Platelet reactivity (PRU) and inhibition (%) were measured with VerifyNow P2Y12 assay in blood samples collected from patients who took a standard dose of clopidogrel (75 mg/d) for at least 7 days.CYP2C19*2 and CYP2C19*17 polymorphism were detected by means of polymerase chain reaction.The distribution and allele frequency difference of CYP2C19*2 (rs4244285) and CYP2C19*17 (rs12248560) genotype in responder group and in non-responder group were compared.Results 104 (30%) patients were non-responders and 243 (70%) patients were responders,according to the patients with PRU values >208 as non-responsiveness to clopidogrel therapy.CYP2C19*2 (rs4244285) wild GG genotype frequencies in 243 clopidogrel response groups and 104 non-response groups was 80.7%,and 54.8%;heterozygous GA was17.3%,and 38.5%;mutant AA was 2.1%,and 6.7% (χ2=7.04,P<0.001).Wild-type Gallele frequency was 89.3%,and 74.0%;mutant Awas 10.7%,and 26.0% (χ2=5.25,P<0.001).CYP2C19*17 (rs12248560) wild CC genotype frequencies was 67.9%,and 75.0%,heterozygous CT was 30.5%,and 23.1%,mutant TT was 1.6%,and 1.9% (χ2=0.81,P=0.388).Wild type Callele frequency was 83.1%,and 84.1%,mutant Tallele frequency was 16.9%,and 13.1% (χ2=0.68,P=0.416).Conclusions Our findings suggest that the CYP2C19*2 polymorphism is associated with non-responsiveness to clopidogrel therapy and the CYP2C19*17 polymorphism enhances antiplatelet activity of clopidogrel.Depending on haplotypes of these two polymorphisms,clopidogrel-treated patients can be protected or not from stent thrombosis and ischaemic events.
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