Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome.
Associations between P2RY12 gene polymorphisms and risks of clopidogrel resistance and adverse cardiovascular events after PCI in patients with acute coronary syndrome.
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DOI：
10.1097/md.0000000000006553
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发表时间：
2017-04
期刊：
影响因子：
1.6
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Li M;Wang H;Xuan L;Shi X;Zhou T;Zhang N;Huang Y
急性冠脉综合征（ACS）患者氯吡格雷抵抗是经皮冠状动脉介入治疗（PCI）后心血管事件复发的主要原因之一。氯吡格雷靶向血小板膜受体P2 RY 12，通过二磷酸腺苷（ADP）抑制血小板聚集。本研究旨在探讨P2 RY 12基因多态性与PCI术后氯吡格雷抵抗和心血管不良事件的关系。从2015年1月至2014年12月，本前瞻性队列研究招募了接受PCI并接受氯吡格雷治疗的ACS患者（N = 498）。 记录患者的人口统计学资料、药物摄入情况和ACS病变情况，并采集全血进行生化检测、ADP诱导的血小板聚集率检测和P2 RY 12基因分型。P2 RY 12基因分型采用聚合酶链反应。通过超声心动图计算左室射血分数。在3至12个月的随访后，记录任何不良CVD事件或死亡的数据。P2 RY 12的C34 T和G52 T的T变异等位基因频率分别为20.3%和11.6%。与野生型基因型患者相比，P2 RY 12基因C34 T或G52 T变异患者发生氯吡格雷抵抗（C34 T：P <0.001; G52 T：P = 0.003）和总心血管事件（C34 T：P = 0.013; G52 T：P =0.018）的风险显著更高。 此外，多变量logistic回归显示，在C34 T（比值比[OR]：2.89（95%置信区间[CI]：1.48-5.64），P = 0.002）和G52 T（OR：3.68 [95% CI：1.71-7.92]，P = 0.001）中具有T变异的患者也具有显著更高的氯吡格雷抵抗风险。 此外，在考虑混杂因素后，C34 T（OR：2.68 [95% CI：1.07-6.73]，P = 0.035）和G52 T（OR：5.64 [95% CI：1.52-20.88]，P = 0.010）的T变异显著增加了PCI后CVD事件的风险。 P2 RY 12基因多态性C34 T和G52 T与中国ACS患者PCI术后氯吡格雷抵抗和后续心血管事件的风险显著相关。
Clopidogrel resistance in patients with acute coronary syndrome (ACS) is one of the key causes of recurrent cardiovascular disease (CVD) events after percutaneous coronary intervention (PCI). Clopidogrel targets the platelet membrane receptor P2RY12 to inhibit platelet aggregation via adenosine diphosphate (ADP). This study aimed to investigate the relationships between P2RY12 polymorphisms and the risk of clopidogrel resistance and adverse CVD events after PCI. From January 2015 to December 2014, patients who had been diagnosed with ACS undergoing PCI and treated with clopidogrel were recruited for this prospective cohort study (N = 498). Data regarding demographics, medication intake, and ACS lesion were recorded, and whole blood samples were collected for biochemical tests, ADP-induced platelet aggregation ratio detection, and P2RY12 genotyping. P2RY12 genotyping was performed by polymerase chain reaction. The left ventricular ejection fraction was calculated by echocardiography. After 3 to 12 months of follow-up, data regarding any adverse CVD event or death were recorded. The allele frequencies for the T variation alleles in C34T and G52T of P2RY12 were 20.3% and 11.6%, respectively. Patients with T variations at C34T or G52T of P2RY12 had a significantly higher risk of clopidogrel resistance (C34T: P < 0.001; G52T: P = 0.003) and total cardiovascular events (C34T: P = 0.013; G52T: P = 0.018) compared to those with the wild-type genotype. Moreover, multivariable logistic regression showed that patients with the T variations in C34T (odds ratio [OR]: 2.89 (95% confidence interval [CI]: 1.48–5.64), P = 0.002) and G52T (OR: 3.68 [95% CI: 1.71–7.92], P = 0.001) also had a significantly higher risk of clopidogrel resistance. Also, the T variations in C34T (OR: 2.68 [95% CI: 1.07–6.73], P = 0.035) and G52T (OR: 5.64 [95% CI: 1.52–20.88], P = 0.010) significantly increased the risk of post-PCI CVD events after accounting for confounding factors. The P2RY12 gene polymorphisms C34T and G52T were significantly associated with a higher risk of clopidogrel resistance and sequential cardiovascular events in Chinese ACS patients after PCI.