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纤溶酶原激活物抑制物-1 4G/5G 多态性与冠心病患者血浆水平的相关性。

PAI-1 4G/5G polymorphism and plasma levels association in patients with coronary artery disease.

机构信息

Departamento de Medicina e Enfermagem, Universidade Federal de Viçosa, Viçosa, MG, Brazil.

出版信息

Arq Bras Cardiol. 2011 Dec;97(6):462-389. doi: 10.1590/s0066-782x2011005000110. Epub 2011 Oct 21.

DOI:10.1590/s0066-782x2011005000110
PMID:22011808
Abstract

BACKGROUND

Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism may influence the PAI-1 expression. High plasma levels of PAI-1 are associated with coronary artery disease (CAD).

OBJECTIVE

This study investigated the influence of PAI-1 4G/5G polymorphism on plasma PAI-1 levels and its association with CAD assessed by coronary angiography.

METHODS

Blood sample of 35 individuals with angiographically normal coronary arteries, 31 individuals presenting mild/moderate atheromatosis, 57 individuals presenting severe atheromatosis and 38 healthy individuals (controls) were evaluated. In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Plasma PAI-1 levels were quantified by ELISA assay (American Diagnostica).

RESULTS

No difference was found between groups regarding age, gender and body mass index. Plasma PAI-1 levels and 4G/4G genotype frequency were significantly higher in the severe atheromatosis group compared to the other groups (p<0.001). Furthermore, patients with 4G/4G genotype (r=0.28, p<0.001) had significantly higher plasma PAI-1 levels than those with 5G/5G genotype (r=0.02, p=0.4511). In addition, in a multiple logistic regression model, adjusted for all the other variables, PAI-1 was observed to be independently associated with CAD > 70% (p<0.001).

CONCLUSION

The most important finding of this study was the association between 4G/4G genotype, high plasma PAI-1 levels and coronary stenosis higher than 70% in Brazilian individuals. Whether high plasma PAI-1 levels are a decisive factor for atherosclerosis worsening or it is a consequence remains to be established.

摘要

背景

1 型纤溶酶原激活物抑制剂(PAI-1)4G/5G 多态性可能影响 PAI-1 的表达。高血浆 PAI-1 水平与冠状动脉疾病(CAD)有关。

目的

本研究探讨了 PAI-1 4G/5G 多态性对血浆 PAI-1 水平的影响及其与冠状动脉造影评估的 CAD 的关系。

方法

对 35 名冠状动脉造影正常的个体、31 名有轻度/中度动脉粥样硬化的个体、57 名有严重动脉粥样硬化的个体和 38 名健康个体(对照组)的血样进行了评估。在患者和对照组中,通过使用等位基因特异性引物的 PCR 扩增来确定 PAI-1 4G/5G 多态性。通过 ELISA 测定法(美国诊断学公司)定量血浆 PAI-1 水平。

结果

各组之间在年龄、性别和体重指数方面无差异。与其他组相比,严重动脉粥样硬化组的血浆 PAI-1 水平和 4G/4G 基因型频率显著更高(p<0.001)。此外,与 5G/5G 基因型(r=0.02,p=0.4511)相比,4G/4G 基因型的患者(r=0.28,p<0.001)的血浆 PAI-1 水平显著更高。此外,在调整所有其他变量的多元逻辑回归模型中,PAI-1 与 CAD >70%(p<0.001)独立相关。

结论

本研究的重要发现是巴西个体中 4G/4G 基因型、高血浆 PAI-1 水平与冠状动脉狭窄程度大于 70%之间的关联。高血浆 PAI-1 水平是动脉粥样硬化恶化的决定因素还是后果仍有待确定。

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