CYP2C19 和 P2Y12 共存多态性对接受支架置入冠状动脉介入治疗的急性冠状动脉综合征患者氯吡格雷反应性和临床结局的影响。

Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention.

机构信息

Department of Cardiology, Fu Wai Hospital and Cardiovascular Institute, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

出版信息

Chin Med J (Engl). 2013 Mar;126(6):1069-75.

PMID:23506580

Abstract

BACKGROUND

The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients.

METHODS

In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.

RESULTS

Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%).

CONCLUSION

Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

摘要

背景

CYP2C19 G681A 单态性已被证明会影响氯吡格雷的反应性。然而，在中国人群中，其他基因共存多态性的影响尚未报道。本研究旨在探讨 CYP2C19 和 P2Y12 共存多态性对中国急性冠脉综合征患者氯吡格雷反应性和不良临床事件的影响。

方法

577 例因急性冠脉综合征行支架置入术的汉族患者采用血栓弹力图评估血小板反应性，并采用连接酶检测反应检测 CYP2C19 G681A 和 P2Y12 C34T 多态性。主要临床终点包括心血管死亡、非致死性心肌梗死、靶血管血运重建和支架血栓形成。次要临床终点为心肌梗死溶栓出血。随访时间为 12 个月。

结果

基因分型显示 194 例 CYP2C19 野生型 GG 基因型和 P2Y12 野生型 CC 基因型携带者（组 1）、102 例 CYP2C19 野生型 GG 基因型和 P2Y12 突变 T 等位基因携带者（组 2）、163 例 CYP2C19 突变 A 等位基因和 P2Y12 野生型 CC 基因型携带者（组 3）、118 例 CYP2C19 突变 A 等位基因和 P2Y12 突变 T 等位基因携带者（组 4）。组 4 的 ADP 抑制率最低（49.74±32.61），氯吡格雷低反应率最高（29.7%）。组 4 的复合主要临床终点发生率高于其他三组（8.5%）；组 2（2.9%）和组 3（3.7%）的复合主要终点发生率与组 1（1.5%）无显著差异。