Li Shao-nan, Liu Zhen, Luo Yi, Chen Ping-an, Lei Xiao-ming, Li Guang-lian
Medical College of Jinan University, Guangzhou 510632, China.
Email:
Zhonghua Nei Ke Za Zhi. 2013 Nov;52(11):961-5.
To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and clopidogrel resistance(CR) in patients with acute coronary syndrome(ACS), and to assess the effects of genetic polymorphism at CYP2C19 (681G>A) on the prognosis of ACS patients.
A total of 462 patients with ACS were enrolled and received loading dose clopidogrel(600 mg). The blood samples of patients were collected before and 24 hours after taking loading dose clopidogrel, then 5 µmol/L ADP-induced platelet aggregation ratio (PAR) was examined. Difference of two PAR ≤ 10% was defined as CR. Genomic DNA of patients were extracted from whole blood samples according to standard protocols and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the single nucleotide polymorphism of the CYP2C19 681G>A. According to whether the gene CYP2C19 681A was carried, patients were divided into two groups: wild type group and non-wild type group. After PCI treatment, patients were followed up for 6 months and major cardiac adverse events (MACE) happened during follow-up periods were recorded.
Totally 127 enrolled cases were finally defined as CR (27.5%) , the frequency of CYP2C19 681A in patients with CR was higher than that in patients without CR (46.9% vs 28.1%, P < 0.01) . The ratio of CR in wild type group were lower than non-wide type group (17.4% vs 36.1%, P < 0.01) . Binary logistic regression analysis indicated that gene CYP2C19 681A was a strong independent predictor for CR in patients with ACS (OR 3.642, P < 0.05). After 6 months of follow-up, Kaplan-Meier survival analysis showed patients of wild type group and non-wild type group had significantly different cumulative non-events survival rates (94.8% vs 89.6%, Log rank = 4.296, P = 0.038) .
The genetic polymorphism of CYP2C19 was associated with CR in patients with ACS. The mutation of CYP2C19 gene increased the risk of MACE in ACS patients undergoing PCI treatments and affected the patients' prognosis.
探讨急性冠状动脉综合征（ACS）患者细胞色素P450（CYP）2C19基因多态性与氯吡格雷抵抗（CR）的关系，并评估CYP2C19（681G>A）基因多态性对ACS患者预后的影响。
共纳入462例ACS患者，给予负荷剂量氯吡格雷（600 mg）。在服用负荷剂量氯吡格雷前及服药后24小时采集患者血样，检测5 μmol/L ADP诱导的血小板聚集率（PAR）。两次PAR差值≤10%定义为CR。按照标准方案从全血样本中提取患者基因组DNA，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对CYP2C19 681G>A单核苷酸多态性进行基因分型。根据是否携带CYP2C19 681A基因，将患者分为两组：野生型组和非野生型组。PCI治疗后，对患者进行6个月随访，记录随访期间发生的主要心脏不良事件（MACE）。
最终共127例入选病例被定义为CR（27.5%），CR患者中CYP2C19 681A基因频率高于非CR患者（46.9%对28.1%，P<0.01）。野生型组CR比例低于非野生型组（17.4%对36.1%，P<0.01）。二元logistic回归分析表明，CYP2C19 681A基因是ACS患者CR的强独立预测因子（OR 3.642，P<0.05）。随访6个月后，Kaplan-Meier生存分析显示野生型组和非野生型组患者的累积无事件生存率有显著差异（94.8%对89.6%，Log rank = 4.296，P = 0.038）。
CYP2C19基因多态性与ACS患者的CR相关。CYP2C19基因突变增加了接受PCI治疗的ACS患者发生MACE的风险，并影响患者预后。
