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急性心肌梗死患者溶栓治疗后血浆纤溶酶原激活物抑制剂1浓度升高与PAI-1基因的4G/5G多态性相关。

Increase in plasma plasminogen activators inhibitor type 1 concentration after fibrinolytic treatment in patients with acute myocardial infarction is associated with 4G/5G polymorphism of PAI-1 gene.

作者信息

Mlynarska A, Waszyrowski T, Kasprzak J D

机构信息

Department of Cardiology, Jonscher Hospital, Lodz, Poland.

出版信息

J Thromb Haemost. 2006 Jun;4(6):1361-6. doi: 10.1111/j.1538-7836.2006.01990.x.

Abstract

BACKGROUND

Preliminary data suggest that plasma concentration of plasminogen activators inhibitor type 1 (PAI-1) is genetically determined and may be related to differential regulation of plasma PAI-1 concentration at baseline and after stimulation.

AIM

This study aimed to evaluate whether increase in the plasma PAI-1 antigen concentration or activity after fibrinolytic therapy in patients with acute myocardial infarction is associated with the -675 4G/5G genetic polymorphism in the promoter region of PAI-1 gene.

RESULTS & CONCLUSIONS: Our study revealed that a rebound effect is observed in PAI-1 activity (ActPAI-1) and PAI-1 antigen (AgPAI-1) concentration after standard streptokinase treatment with maximal values of 3 h (t3) after the completion of streptokinase infusion. Both ActPAI-1 and AgPAI-1 were significantly higher at t3 compared to the levels before fibrinolytic treatment: 37.3 (20.0-67.7) vs. 10.0 (3.6-26.0) IU L(-1); P = 0.00001 and 29.9 (15.6-42.3) vs. 20.9 (13.0-30.2) ng mL(-1); P = 0.001, respectively. The stratification of the patients by genotype revealed that carriers of the 4G allele had higher concentrations of PAI-1 antigen 3 h after streptokinase infusion: 30.9 vs. 13.8 ng mL(-1); P = 0.019. No significant association between PAI-1 activity and genotype was found. In conclusion, the rebound effect in serum PAI-1 concentration observed after streptokinase treatment may be related to the 4G/5G polymorphism in the PAI-1 gene promoter.

摘要

背景

初步数据表明,纤溶酶原激活物抑制剂1(PAI-1)的血浆浓度由基因决定,可能与基线及刺激后血浆PAI-1浓度的差异调节有关。

目的

本研究旨在评估急性心肌梗死患者溶栓治疗后血浆PAI-1抗原浓度或活性的升高是否与PAI-1基因启动子区域-675 4G/5G基因多态性相关。

结果与结论

我们的研究显示,标准链激酶治疗后PAI-1活性(ActPAI-1)和PAI-1抗原(AgPAI-1)浓度出现反弹效应,在链激酶输注结束后3小时(t3)达到最大值。与溶栓治疗前相比,t3时ActPAI-1和AgPAI-1均显著升高:分别为37.3(20.0 - 67.7)对10.0(3.6 - 26.0)IU L(-1);P = 0.00001和29.9(15.6 - 42.3)对20.9(13.0 - 30.2)ng mL(-1);P = 0.001。按基因型对患者进行分层显示,4G等位基因携带者在链激酶输注后3小时的PAI-1抗原浓度更高:30.9对13.8 ng mL(-1);P = 0.019。未发现PAI-1活性与基因型之间存在显著关联。总之,链激酶治疗后血清PAI-1浓度的反弹效应可能与PAI-1基因启动子中的4G/5G多态性有关。

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