Iwai N, Shimoike H, Nakamura Y, Tamaki S, Kinoshita M
1st Department of Internal Medicine, Shiga University of Medical Science, Japan.
Atherosclerosis. 1998 Jan;136(1):109-14. doi: 10.1016/s0021-9150(97)00191-3.
The 4G allele of the plasminogen activator inhibitor (PAI-I) gene is associated with increased PAI-I levels. Increased PAI-I levels have been reported to be associated with atherothrombotic events. However, the significance of the 4G/5G polymorphism of the PAI-I gene in the pathogenesis of ischemic heart diseases has not been determined. We assessed the 4G/5G polymorphism of the PAI-I gene in 500 subjects including 148 normal controls, 23 subjects with normal coronary arteries, 28 subjects with a paradoxical acetylcholine response, 97 subjects with angina pectoris (AP) and 204 subjects with myocardial infarction (MI). We assessed the length of time between the first anginal pain and the onset of acute coronary syndromes (ACS) in the AP and MI subjects. Subjects who developed ACS within 2 months from the first anginal pain were categorized to have a rapid progression to ACS, and subjects who had had stable anginal pain more than 2 months were placed in the non-ACS group. Subjects in the ACS group were younger than those in non-ACS group (P = 0.012) The frequency of the 5G/5G genotype of the PAI-I gene was lower in the ACS (0.228) than in the non-ACS group (0.093) (P = 0.003). Multiple logistic analyses revealed that a younger age (P = 0.028, odds ratio = 1.03) and the (4G/5G + 4G/4G) genotype of the PAI-I gene (P = 0.008, odds ratio = 2.68) were associated with the ACS group. We also assessed plasma PAI-I antigen levels in 78 subjects. Plasma PAI-I antigen levels in the non-ACS group were significantly lower than those in the ACS group (P = 0.050). Multiple regression analyses revealed that plasma PAI-I levels were determined by plasma insulin (P < 0.001) and the genotype of the PAI-I gene (P = 0.019). Higher plasma insulin levels and the (4G/5G + 4G/4G) genotype of the PAI-I gene were associated with higher plasma PAI-I levels. The 4G/5G polymorphism of the PAI-I gene influenced not only plasma PAI-I antigen levels but also the time course of the progression to ACS in patients with coronary atherosclerosis.
纤溶酶原激活物抑制剂（PAI-1）基因的4G等位基因与PAI-1水平升高有关。据报道，PAI-1水平升高与动脉粥样硬化血栓形成事件有关。然而，PAI-1基因的4G/5G多态性在缺血性心脏病发病机制中的意义尚未确定。我们评估了500名受试者PAI-1基因的4G/5G多态性，其中包括148名正常对照者、23名冠状动脉正常者、28名乙酰胆碱反应异常者、97名心绞痛（AP）患者和204名心肌梗死（MI）患者。我们评估了AP和MI患者首次心绞痛发作至急性冠状动脉综合征（ACS）发作之间的时间长度。在首次心绞痛发作后2个月内发生ACS的受试者被归类为ACS快速进展者，而心绞痛稳定超过2个月的受试者被归入非ACS组。ACS组的受试者比非ACS组的受试者年轻（P = 0.012）。PAI-1基因5G/5G基因型的频率在ACS组（0.228）低于非ACS组（0.093）（P = 0.003）。多因素逻辑分析显示，年龄较小（P = 0.028，比值比 = 1.03）和PAI-1基因的（4G/5G + 4G/4G）基因型（P = 0.008，比值比 = 2.68）与ACS组相关。我们还评估了78名受试者的血浆PAI-1抗原水平。非ACS组的血浆PAI-1抗原水平显著低于ACS组（P = 0.050）。多因素回归分析显示，血浆PAI-1水平由血浆胰岛素（P < 0.001）和PAI-1基因的基因型（P = 0.019）决定。较高的血浆胰岛素水平和PAI-1基因的（4G/5G + 4G/4G）基因型与较高的血浆PAI-1水平相关。PAI-1基因的4G/5G多态性不仅影响血浆PAI-1抗原水平，还影响冠状动脉粥样硬化患者进展至ACS的时间进程。
