Gardemann A, Lohre J, Katz N, Tillmanns H, Hehrlein F W, Haberbosch W
Institut für Klinische Chemie und Pathobiochemie, Bad Nauheim, Germany.
Thromb Haemost. 1999 Sep;82(3):1121-6.
Disturbances in fibrinolytic activity, such as increase in plasminogen activator inhibitor (PAI) activity, have been linked with an increased risk for coronary artery disease (CAD) and myocardial infarction (MI). Since 4G4G homozygotes of an insertion/deletion (4G/5G) gene variation in the promoter of PAI-I have been shown to have increased levels of PAI-I, we analysed the relation of this gene polymorphism to CAD and MI in a population of 2565 participants who underwent coronary angiography for diagnostic purposes.
In the total sample, the PAI-I 4G/4G genotype was associated with the presence, but not with the extent of CAD. However, in a subgroup of former and present smokers (n = 1782) or of individuals with a BMI above the mean value of 26.9 kg x m(-2) (n = 1269), the PAI-I 4G4G genotype was not only associated with the presence, but also with the extent of CAD, defined either by the number of diseased vessels or by the CHD score according to Gensini. This observation also applied to other high-risk groups of individuals with high BMI and hypertension (n = 869), of subjects with high fibrinogen plasma levels (>3.53 g x l(-1), mean value) and hypertension (n = 599) and of former and present smokers with high fibrinogen and hypertension (n = 452). An association of the gene variation with MI was not detected.
The present data indicate that the 4G/4G genotype of the PAI-I gene polymorphism is an independent risk factor for coronary artery disease and that the additional presence of major cardiovascular risk factors accelerates the risk for this disease.
纤溶活性紊乱，如纤溶酶原激活物抑制剂（PAI）活性增加，与冠状动脉疾病（CAD）和心肌梗死（MI）风险增加有关。由于PAI-1启动子插入/缺失（4G/5G）基因变异的4G4G纯合子已被证明PAI-1水平升高，我们在2565名因诊断目的接受冠状动脉造影的参与者群体中分析了这种基因多态性与CAD和MI的关系。
在整个样本中，PAI-1 4G/4G基因型与CAD的存在有关，但与CAD的严重程度无关。然而，在既往或当前吸烟者亚组（n = 1782）或体重指数（BMI）高于平均值26.9 kg·m⁻²的个体亚组（n = 1269）中，PAI-1 4G4G基因型不仅与CAD的存在有关，还与CAD的严重程度有关，CAD严重程度通过病变血管数量或根据Gensini评分的冠心病评分来定义。这一观察结果也适用于其他高危个体群体，包括高BMI和高血压患者（n = 869）、血浆纤维蛋白原水平高（>3.53 g·L⁻¹，平均值）且患有高血压的受试者（n = 599）以及纤维蛋白原水平高且患有高血压的既往或当前吸烟者（n = 452）。未检测到该基因变异与MI有关。
目前的数据表明，PAI-1基因多态性的4G/4G基因型是冠状动脉疾病的独立危险因素，主要心血管危险因素的额外存在会加速该疾病的风险。
