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冠心病患者氯吡格雷低反应性与CYP2C19基因多态性的相关性研究

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目的 探索冠状动脉粥样硬化性心脏病(冠心病)患者氯吡格雷低反应与CYP450酶中
CYP2C19基因型多态性之间的相关性。方法 搜集2015年3月至2018年9月于首都医科大学宣武医院心脏
科确诊的冠心病患者680例,根据血栓弹力图(TEG)检测二磷酸腺苷(ADP)诱导的血小板抑制率是否
低于30%分为氯吡格雷低反应组(CLR)及氯吡格雷正常反应组(NCLR),同时检测CYP2C19基因型,
并根据CYP2C19基因型分为快代谢(CYP2C19*1*1)、中等代谢(CYP2C19*1*2、CYP2C19*1*3)、慢
代谢(CYP2C19*2*2、CYP2C19*2*3、CYP2C19 *3*3)3种类型。分析氯吡格雷低反应性与CYP2C19基
因型之间的关系。结果 ①680例患者中氯吡格雷低反应组304例(44.7%),氯吡格雷正常反应组376例
(55.3%),两组一般资料如年龄、体质指数(BMI)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋
白胆固醇(LDL-C)、高血压、糖尿病等均无统计学差异(P>0.05),而性别、吸烟史、饮酒史、血
小板计数、谷草转氨酶、三酰甘油等比较,差异具有统计学意义(P<0.05)。②两组间CYP2C19基因多
态性差异具有统计学意义(P<0.05)。③3类CYP2C19基因型间氯吡格雷低反应性差异,差异具有统计
学意义(P<0.05);快代谢型与中等代谢型及慢代谢型比较均有统计学意义(P<0.05),而中等代谢
型和慢代谢型比较差异无统计学意义(P=0.063)。④通过多因素Logistic回归分析发现血小板计数、谷
草转氨酶及CYP2C19基因多态性与氯吡格雷低反应有相关性(P<0.05)。⑤根据ROC曲线,发现通过检
测CYP2C19基因型对氯吡格雷的药物反应性有预测作用。结论 冠心病患者服用氯吡格雷产生低反应与
CYP2C19基因型多态性有相关性,检测CYP2C19基因型对临床抗血小板药物的应用具有指导性意义。

Abstract:

Objective To study the correlation between clopidogrel low responsiveness (CLR) and CYP2C19
gene polymorphism in CYP450 enzyme in patients with coronary heart disease (CHD). Methods CHD patients (n=680)
were chosen from Department of Cardiology in Xuanwu Hospital affiliated to Capital University of Medical Sciences
from Mar. 2015 to Sept. 2018. All patients were divided, according to whether or not adenosine diphosphate (ADP)
-induced platelet inhibition rate below 30% detected by using thrombelastogram (TEG), into CLR group and non-CLR
group (NCLR group). At the same time, the genotypes of CYP2C19 were detected, and divided, according to genotypes
of CYP2C19, into fast metabolism type (CYP2C19*1*1), moderate metabolism type (CYP2C19*1*2, CYP2C19*1*3)
and slow metabolism type (CYP2C19*2*2, CYP2C19*2*3, CYP2C19*3*3). The relationship between CLR and
genotypes of CYP2C19 was analyzed. Results ①Among 680 patients, there were 304 (44.7%) in CLR group and 376
(55.3%) in NCLR group. The general data including age, body mass index (BMI), high-density lipoprotein-cholesterol
(HDL-C), low-density lipoprotein-cholesterol (LDL-C), hypertension and diabetes had no statistical difference
(P>0.05), and sex, smoking history, drinking history, platelet count, glutamic oxalacetic transaminase (GOT) and
triglyceride (TG) had statistical difference (P<0.05) in 2 groups. ②The difference in CYP2C19 gene polymorphism
had statistical significance between 2 groups (P<0.05). ③The difference in CLR had statistical significance among 3
genotypes of CYP2C19 (P<0.05). The comparisons among fast metabolism type, moderate metabolism type and slow
metabolism type had statistical significance (P<0.05), and difference between moderate metabolism type and slow
metabolism type had no statistical significance (P=0.063). ④The results of multi-factor Logistic regression analysis
showed that platelet count, GOT and CYP2C19 gene polymorphism had correlation (P<0.05). ⑤Based on ROC

analysis, the detection of genotypes of CYP2C19 had predictive effect on clopidogrel responsiveness. Conclusion

CLR is correlated to CYP2C19gene polymorphism in CHD patients, and detection of CYP2C19 gene polymorphism has
a guiding significance to clinical application of antiplatelet drugs.

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