CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation
CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation
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DOI：
10.2217/14622416.9.9.1251
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发表时间：
2008-09-01
期刊：
影响因子：
2.1
通讯作者：
Schwab, Matthias
中科院分区：
文献类型：
--
作者：
Geisler, Tobias;Schaeffeler, Elke;Schwab, Matthias
目的：探讨冠心病患者对负荷剂量氯吡格雷的反应性与细胞色素P450（P450）2C 19基因型、其他同工酶和非遗传因素的关系。材料和方法：对接受经皮冠状动脉介入治疗的患者（n = 237）进行了CYP 2C 19（*2 *3和 *17）、CYP 3A 4 *1B和CYP 3A 5 *3变体的基因分型。在首次给予600 mg氯吡格雷后测定二磷酸腺苷诱导的血小板聚集。结果如下：与非携带者相比，CYP 2C 19 *2携带者显示残余血小板聚集（RPA）显著增加（OR：4.6; 95% CI：2.5-8.7; p < 0.0001）。其他多态性对RPA无影响。为了开发更好预测RPA的风险评分，分析了CYP 2C 19 *2基因型和先前确定的非遗传风险因素（年龄>65岁，2型糖尿病，左心室功能下降，肾衰竭和急性冠状动脉综合征）。多变量logistic回归分析显示非遗传因素（卡方2 = 5.32; p = 0.021）和CYP 2C 19 *2（卡方2 = 21.31; p < 0.0001）与高RPA显著相关，并且两者联合使用的相关性更高（卡方2 = 25.85; p < 0.0001）。结论：通过将CYP 209 *2基因型加入非遗传性危险因素中，可显著改善氯吡格雷负荷剂量后反应性的预测。
Aims: To investigate an association of responsiveness to clopidogrel loading dose with genotypes of cytochrome P450 (CYP) 2C19, other CYP isozymes and nongenetic factors in patients with coronary artery disease. Materials & methods: Genotyping for CYP2C19 (*2 *3 and *17), CYP3A4*1B and CYP3A5*3 variants was performed in patients (n = 237) who underwent percutaneous coronary intervention. Adenosine diphosphate-induced platelet aggregation was determined after first administration of 600 mg clopidogrel. Results: CYP2C19*2 carriers showed significantly increased residual platelet aggregation (RPA) (OR: 4.6; 95% CI: 2.5-8.7; p < 0.0001) compared with noncarriers. All other polymorphisms had no influence on RPA. For the development of a risk score for better prediction of RPA, CYP2C19*2 genotype and previously identified nongenetic risk factors (age >65 years, Type 2 diabetes mellitus, decreased left ventricular function, renal failure and acute coronary syndrome) were analyzed. Multivariable logistic regression analysis showed a significant correlation of the nongenetic factors (chi 2 = 5.32; p = 0.021) and CYP2C19*2 (chi 2 = 21.31; p < 0.0001) with high RPA, and an even higher association for the combination of both (chi 2 = 25.85; p < 0.0001). Conclusions: Prediction of responsiveness after clopidogrel loading dose may substantially be improved by adding CYP209*2 genotype to nongenetic risk factors.