Sigusch H H, Vogt S, Gruber U, Reinhardt D, Lang K, Surber R, Farker K, Müller S, Hoffmann A
Institute of Clinical Pharmacology, University of Jena, Germany.
Scand J Clin Lab Invest. 1997 Apr;57(2):127-32. doi: 10.1080/00365519709056380.
Coronary artery disease (CAD) is a polygenic disease whose phenotypic manifestation depends on the interaction of a number of environmental factors. A number of genes, including the angiotensin-I-converting enzyme (ACE) gene, have been implicated in the pathogenesis of CAD. ACE could affect smooth muscle cell and fibroblast migration and proliferation, low-density lipoprotein (LDL) oxidation and endothelial cell function; these are all important factors in atherosclerosis. A polymorphic variant of the ACE gene correlates with higher circulating ACE levels and carries an increased risk of myocardial infarction, and cardiomyopathies. In this study, we sought to determine the distribution of ACE genotypes and the frequency of allele D in patients undergoing coronary angiography at our institution. DNA from 196 patients with angiographically proven CAD and 96 controls without CAD was amplified by polymerase chain reaction (PCR). The primers flanked the region of the ACE gene (intron 16) where the insertion (I) or deletion (D) of a 287-bp fragment results in the I/D polymorphism. PCR amplification of alleles I and D resulted in 490- and 190-bp products, respectively. In the control group, the relative allele frequencies of the polymorphism were similar to those of previously published European studies. The ACE genotype DD was present in 37.3% of patients with CAD as compared to 23.4% in the controls (p < 0.001, odds ratio 1.95, 95% confidence intervals (CI) 1.06-3.57). There was no association with the history of prior myocardial infarction. The genotype distribution in patients with single-vessel involvement was not significantly different from controls (p = 0.14). However, the DD genotype was significantly more common in patients having multivessel CAD when compared to single-vessel disease, indicating an association of this polymorphism with the extent of CAD. ACE genotype DD is more common in patients with multivessel CAD as compared to controls and to patients with single-vessel involvement, indicating that genotype DD is a genetic risk factor for extensive, multivessel CAD.
冠状动脉疾病（CAD）是一种多基因疾病，其表型表现取决于多种环境因素的相互作用。包括血管紧张素转换酶（ACE）基因在内的许多基因都与CAD的发病机制有关。ACE可影响平滑肌细胞和成纤维细胞的迁移与增殖、低密度脂蛋白（LDL）氧化以及内皮细胞功能；这些都是动脉粥样硬化的重要因素。ACE基因的一种多态性变体与循环中ACE水平升高相关，并增加了心肌梗死和心肌病的风险。在本研究中，我们试图确定在我们机构接受冠状动脉造影的患者中ACE基因型的分布以及等位基因D的频率。通过聚合酶链反应（PCR）扩增了196例经血管造影证实患有CAD的患者和96例无CAD的对照者的DNA。引物位于ACE基因（内含子16）区域两侧，该区域287 bp片段的插入（I）或缺失（D）导致I/D多态性。等位基因I和D的PCR扩增分别产生490 bp和190 bp的产物。在对照组中，该多态性的相对等位基因频率与先前发表的欧洲研究结果相似。CAD患者中37.3%存在ACE基因型DD，而对照组为23.4%（p<0.001，优势比1.95，95%置信区间（CI）1.06 - 3.57）。与既往心肌梗死病史无关。单支血管受累患者的基因型分布与对照组无显著差异（p = 0.14）。然而，与单支血管疾病相比，多支血管CAD患者中DD基因型明显更常见，表明这种多态性与CAD的范围有关。与对照组和单支血管受累患者相比，多支血管CAD患者中ACE基因型DD更常见，表明基因型DD是广泛多支血管CAD的遗传危险因素。
