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细胞色素 2C19*2 和 *3 等位基因在接受择期经皮冠状动脉介入治疗的东亚患者中同样减弱氯吡格雷的反应。

The cytochrome 2C19*2 and *3 alleles attenuate response to clopidogrel similarly in East Asian patients undergoing elective percutaneous coronary intervention.

机构信息

Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea.

出版信息

Thromb Res. 2011 Jan;127(1):23-8. doi: 10.1016/j.thromres.2010.10.021.

DOI:10.1016/j.thromres.2010.10.021
PMID:21075428
Abstract

INTRODUCTION

Carriage of CYP2C192 allele is associated with diminished platelet response to clopidogrel. However, the loss-of-function impact of CYP2C193 allele on antiplatelet effect of clopidogrel has not been definitely verified. We conducted this study to compare decreased response to clopidogrel according to carriage of CYP2C19*2 vs. *3 allele.

MATERIALS AND METHODS

The study included 190 consecutive Korean patients undergoing elective percutaneous coronary intervention. Light transmittance aggregometry and the VerifyNow P2Y(12) assay were used to assess platelet reactivity (PR) at least 12 hours after 300-mg loading of clopidogrel. The cutoff of high on-treatment PR (HPR) was defined as 5 μmol/L ADP-induced PR >50%. CYP2C19 genotype was analyzed by the SNaPshot method.

RESULTS

Carriers of at least one CYP2C19 variant allele were 115 patients (60.5%), and allelic frequency of CYP2C19*2 and 3 was 30.3% and 6.8%, respectively. PR and the rate of HPR increased proportionally according to the number of CYP2C19 variant allele. Carriage of CYP2C19 variant allele was an only independent predictor of HPR in multivariate analysis. When we compare the effect of allelic carriage, there were no significant differences in platelet measures and the rate of HPR between carriers of CYP2C192 and/or *3 allele(s) whether they were intermediate or poor metabolizers.

CONCLUSION

Carriage of CYP2C193 allele is associated with diminished antiplatelet effect of clopidogrel, which may be as potent as the loss-of-function effect of CYP2C192 allele.

摘要

简介

CYP2C192 等位基因的携带与氯吡格雷的血小板反应减弱有关。然而,CYP2C193 等位基因对氯吡格雷抗血小板作用的失活影响尚未得到明确验证。我们进行这项研究是为了比较根据 CYP2C192 与3 等位基因携带情况,氯吡格雷反应降低的情况。

材料与方法

这项研究纳入了 190 例连续的韩国择期行经皮冠状动脉介入治疗的患者。在氯吡格雷负荷 300mg 至少 12 小时后,采用光透射聚集法和 VerifyNow P2Y(12)检测法评估血小板反应性(PR)。高治疗期 PR(HPR)的截止值定义为 5μmol/L ADP 诱导的 PR>50%。CYP2C19 基因型采用 SNaPshot 法进行分析。

结果

至少携带一个 CYP2C19 变异等位基因的患者有 115 例(60.5%),CYP2C192 和3 的等位基因频率分别为 30.3%和 6.8%。PR 和 HPR 的发生率随 CYP2C19 变异等位基因数量的增加而呈比例增加。在多变量分析中,CYP2C19 变异等位基因的携带是 HPR 的唯一独立预测因子。当我们比较等位基因携带的效果时,在中间代谢型或弱代谢型患者中,携带 CYP2C192 和/或3 等位基因的患者,其血小板指标和 HPR 的发生率均无显著差异。

结论

CYP2C193 等位基因的携带与氯吡格雷的抗血小板作用减弱有关,其作用可能与 CYP2C192 等位基因的失活作用相当。

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