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血小板P2Y12单倍型与慢性冠心病心血管事件风险之间的关联。

Association between platelet P2Y12 haplotype and risk of cardiovascular events in chronic coronary disease.

作者信息

Schettert Isolmar T, Pereira Alexandre C, Lopes Neuza H, Hueb Whady A, Krieger Jose E

机构信息

Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.

出版信息

Thromb Res. 2006;118(6):679-83. doi: 10.1016/j.thromres.2005.11.009. Epub 2006 Jan 6.

Abstract

INTRODUCTION

A positive association was recently described between P2Y12 platelet receptor H1 and H2 haplotypes and peripheral artery disease. We tested the described P2Y12 receptor haplotypes in a group of patients with coronary artery disease.

STUDY DESIGN AND METHODS

The P2Y12 platelet receptor H1 and H2 haplotypes was tested in a group of 540 patients enrolled in the Medical, Angioplasty, or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. After a 3-year follow-up period, the incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization was determined in the H1/H1, H1/H2 and H2/H2 haplotype groups. We used Student's t-test and the chi-square test to analyze the differences among groups and Kaplan-Meier method to calculate survival curves. Risk was assessed with the use of a Cox proportional-hazards model.

RESULTS

The frequency of haplotypes among studied patients were 410 (75.9%) H1/H1, 119 (22.0%) H1/H2 and 11 (2.1%) H2/H2. The baseline clinical characteristics, mean clinical follow-up time and received treatment of each genotype group were similar. We did not disclose any association between haplotype groups regarding the incidence of any of the studied cardiovascular end-points.

CONCLUSION

This is the first report studying the association of P2Y12 platelet receptor H1 and H2 haplotype and cardiovascular events. Our findings do not provide evidence for a strong association between H1/H1 and H1/H2 haplotypes and a increased risk of cardiovascular events in a population with CAD. Future works should address the role of the H2/H2 haplotype as a genetic marker for cardiovascular events.

摘要

引言

最近有研究表明,P2Y12血小板受体H1和H2单倍型与外周动脉疾病之间存在正相关。我们在一组冠心病患者中检测了上述P2Y12受体单倍型。

研究设计与方法

在参加医学、血管成形术或手术研究II(MASS II)的540名患者中检测了P2Y12血小板受体H1和H2单倍型。MASS II是一项随机试验,比较了对冠心病(CAD)且左心室功能保留患者的治疗方法。经过3年的随访期,确定了H1/H1、H1/H2和H2/H2单倍型组中心脏死亡、心肌梗死和需要血管重建的难治性心绞痛复合终点的发生率。我们使用学生t检验和卡方检验分析组间差异,并使用Kaplan-Meier方法计算生存曲线。使用Cox比例风险模型评估风险。

结果

研究患者中H1/H1单倍型的频率为410例(75.9%),H1/H2为119例(22.0%),H2/H2为11例(2.1%)。各基因型组的基线临床特征、平均临床随访时间和接受的治疗相似。我们未发现单倍型组与任何研究的心血管终点发生率之间存在关联。

结论

这是第一项研究P2Y12血小板受体H1和H2单倍型与心血管事件关联的报告。我们的研究结果未提供证据表明H1/H1和H1/H2单倍型与CAD人群中心血管事件风险增加之间存在强关联。未来的研究应探讨H2/H2单倍型作为心血管事件遗传标志物的作用。

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