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浙江大学学报(医学版)  2014, Vol. 43 Issue (3): 333-338    DOI: 10.3785/j.issn.10089292.2014.05.012
原著     
血小板P2Y12受体基因多态性与氯吡格雷抵抗相关性研究
李晓静,陈晓敏
宁波市第一医院心血管内科, 浙江 宁波 315010
Association between clopidogrel resistance and polymorphism of platelet adenosine diphosphate receptor in patients with coronary atherosclerotic disease
LI Xiao-jing,CHEN Xiao-min
Ningbo First Municipal Hospital, Ningbo 315010, China
全文: PDF(733 KB)  
摘要: 

目的:分析临床氯吡格雷抵抗与P2Y12受体基因多态性之间的关系。方法:2011年5月至2012年11月期间在宁波市第一医院心血管内科收治住院并行介入治疗的冠状动脉粥样硬化性心脏病患者共370例,规则使用双联抗血小板治疗(每晚1次阿司匹林 100 mg ,每天1次氯吡格雷75 mg)7 d以上。运用DNA测序技术检测P2Y12受体基因C34T与G52T位点的多态性,分析基因多态性与氯吡格雷抵抗发生率和临床预后的相关性。结果:370例患者出现氯吡格雷抵抗共100例(27%),其中男性36例(36%),女性64例(64%);在C34T位点,CC基因型和CT+TT基因型分别有26例(12.3%)和74例(46.8%)发生氯吡格雷抵抗,两者比较差异有统计学意义(χ2=5.502, P=0.019),术后1年心绞痛复发率CT+TT基因型组高于CC基因型组(χ2=4.956 ,P=0.026);在G52T位点,GG基因型和GT+TT基因型分别有48例(22.1%)和52例(34.2%)发生氯吡格雷抵抗,两者比较差异有统计学意义(χ2=4.350 ,P=0.037),术后1年急诊血运重建术、心绞痛、联合终点事件发生率GT+TT基因型组均高于GG基因型组(均P<0.05)。结论:P2Y12受体基因在34、52位点上的T基因突变可能是产生氯吡格雷抵抗的一个危险因素,同时T基因突变对心血管疾病患者预后有不良影响。

关键词 血小板聚集抑制剂/药理学;噻氯匹定/药理学受体, 嘌呤能P2受体, 嘌呤能P2/血液;多态现象, 遗传;基因    
Abstract

Objective: To investigate the relation of clopidogrel resistance to polymorphism of adenosine diphosphate receptor (P2Y12). Methods: Three hundred and seventy patients with coronary atherosclerotic heart disease, who were admitted in hospital from May 2011 to November 2012 and underwent percutaneous coronary intervention, were enrolled in the study. All patients recieved antiplatelet therapy (oral aspirin 100 mg per night and clopidogrel 75 mg per day for >7 d). The gene polymorphisms of C34T and G52T P2Y12 receptor were detected by using DNA sequencing technique. The relationship of gene polymorphism with the incidence of clopidogrel resistance and clinical outcomes were analyzed. Results: Among 370 patients, clopidogrel resistance developed in 100 cases, including 36 males (36%) and 64 females (64%). In the C34T locus, 212 cases were of CC genotype and 158 were of CT+TT genotype; the incidence of clopidogrel resistance in CC genotype was significantly lower than that in CT+TT genotype (P<0.05). In the G52T locus, 218 cases were of GG genotype and 152 cases were of GT+TT genotype; the incidence of clopidogrel resistance in GT+TT genotype were significantly higher than that in GG genotype (P<0.05). After 1year followup, patients with CC genotype had lower incidence of angina recurrence than patients with CT+TT genetype did (13.2% vs 19.6%, χ2=4.956, P<0.05), and patients with GG genotype had lower incidence of emergency revascularization, angina, and cardiovascular composite endpoint events than patients with GT+TT genotype did (χ2=4.135,6.823,5.916, Ps<0.05). Conclusion: T34, 52 mutations on P2Y12 receptor gene may be a risk factor for clopidogrel resistance and adverse cardiovascular events.

Key wordsPlatelet aggregation inhibitors/pharmacology    Ticlopidine/ pharmacology    Receptors, purinergic P2    Receptors, purinergic P2/blood    Polymorphism, genetic    Genes
收稿日期: 2013-04-26     
通讯作者: 陈晓敏(1963-), 男, 硕士,教授,硕士生导师, 主要从事心血管疾病的介入诊疗与科研;Email:chxmin@hotmail.com   
Corresponding author: CHEN Xiaomin, Email: chxmin@hotmail.com   
作者简介: 李晓静(1984-),女,硕士,主治医师,主要从事抗血小板药物抵抗分子遗传学机制研究; Email: reta_lee@hotmail.com
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引用本文:

李晓静,陈晓敏. 血小板P2Y12受体基因多态性与氯吡格雷抵抗相关性研究[J]. 浙江大学学报(医学版), 2014, 43(3): 333-338.
LI Xiao-jing,CHEN Xiao-min. Association between clopidogrel resistance and polymorphism of platelet adenosine diphosphate receptor in patients with coronary atherosclerotic disease. Journal of ZheJiang University(Medical Science), 2014, 43(3): 333-338.

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http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.10089292.2014.05.012      或      http://www.zjujournals.com/xueshu/med/CN/Y2014/V43/I3/333

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