Kim D K, Kim J W, Kim S, Gwon H C, Ryu J C, Huh J E, Choo J A, Choi Y, Rhee C H, Lee W R
Cardiovascular Institute, Sung Kyun Kwan University, College of Medicine, Seoul, Korea.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3242-7. doi: 10.1161/01.atv.17.11.3242.
The deletion (D) allele of the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene is strongly associated with an increased level of circulating ACE. The ACE gene polymorphism may influence the production of angiotensin II (Ang II). It has been shown that Ang II modulates fibrinolysis, that is, Ang II increases plasminogen activator inhibitor-1 (PAI-1) mRNA and plasma PAI-1 levels in vitro and in vivo. Considered together, we tested the hypothesis that the deletion allele of the ACE gene might be associated with increased levels of PAI-1. We related the ACE genotype to PAI-1 antigen levels in 603 men and 221 women attending a routine health screening. As a whole, the plasma PAI-1 level was not strongly associated with ACE genotype. Since the PAI-1 level was significantly influenced by well-known risk factors for coronary artery disease (CAD), we further analyzed the data after excluding subjects with major cardiovascular risk factors. In low-risk male subjects, the DD genotype had significantly higher levels of plasma PAI-1 (DD: 20.3 +/- 2.2; DI: 13.9 +/- 1.1; II: 13.6 +/- 1.3 ng/mL, P = .010 by ANOVA). In low-risk female subjects, the DD genotype showed a tendency to a high level of plasma PAI-1 without statistical significance. When analysis was restricted to postmenopausal women (age > or = 55 or FSH > or = 35 ng/mL), the DD genotype showed a significantly higher level of PAI-1 than subjects with the DI and II genotypes (27.7 +/- 6.2 versus 15.6 +/- 1.8 ng/mL, P = .028). The DD polymorphism of the ACE gene is associated with high PAI-1 levels in male and possibly in postmenopausal female subjects who have lower conventional cardiovascular risk factors. These results suggest that the increased ACE activity caused by DD polymorphism may play an important role in elevating the level of plasma PAI-1. Our data support the notion that the genetic variation of ACE contributes to the balance of the fibrinolytic pathway.
血管紧张素转换酶（ACE）基因插入/缺失（I/D）多态性的缺失（D）等位基因与循环ACE水平升高密切相关。ACE基因多态性可能影响血管紧张素II（Ang II）的产生。研究表明，Ang II可调节纤维蛋白溶解，即Ang II在体外和体内均可增加纤溶酶原激活物抑制剂-1（PAI-1）的mRNA水平和血浆PAI-1水平。综合考虑，我们检验了ACE基因缺失等位基因可能与PAI-1水平升高相关的假说。我们将ACE基因型与603名男性和221名接受常规健康筛查的女性的PAI-1抗原水平进行了关联分析。总体而言，血浆PAI-1水平与ACE基因型无明显关联。由于PAI-1水平受冠状动脉疾病（CAD）已知危险因素的显著影响，我们在排除具有主要心血管危险因素的受试者后进一步分析了数据。在低风险男性受试者中，DD基因型的血浆PAI-1水平显著更高（DD：20.3±2.2；DI：13.9±1.1；II：13.6±1.3 ng/mL，方差分析P = 0.010）。在低风险女性受试者中，DD基因型的血浆PAI-1水平有升高趋势，但无统计学意义。当分析仅限于绝经后女性（年龄≥55岁或促卵泡激素≥35 ng/mL）时，DD基因型的PAI-1水平显著高于DI和II基因型的受试者（27.7±6.2对15.6±1.8 ng/mL，P = 0.028）。ACE基因的DD多态性与传统心血管危险因素较低的男性以及可能绝经后女性的高PAI-1水平相关。这些结果表明，DD多态性导致的ACE活性增加可能在升高血浆PAI-1水平中起重要作用。我们的数据支持ACE基因变异有助于纤维蛋白溶解途径平衡的观点。
