血管紧张素转换酶基因DD型是冠状动脉疾病的一个风险因素。

Angiotensin-I converting enzyme genotype DD is a risk factor for coronary artery disease.

作者信息

Beohar N, Damaraju S, Prather A, Yu Q T, Raizner A, Kleiman N S, Roberts R, Marian A J

机构信息

Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

出版信息

J Investig Med. 1995 Jun;43(3):275-80.

PMID:7614074

Abstract

BACKGROUND

Coronary artery disease (CAD) is a polygenic disease whose phenotypic manifestation is due to interaction of a number of environmental factors with an underlying genetic background. A number of genes, including the angiotensin-I converting enzyme (ACE) gene, have been implicated in the pathogenesis of CAD. ACE can affect oxidation of LDL, endothelial cell function, and smooth muscle cell migration and proliferation: all important components of atherosclerosis. A variant of ACE gene, genotype DD is associated with a higher plasma level of ACE and 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 with CAD undergoing coronary angioplasty.

METHODS

DNA from 182 white patients undergoing coronary angioplasty and 338 apparently healthy white individuals was amplified by polymerase chain reaction (PCR) in the region of the polymorphism using the previously published protocol.

RESULTS

PCR amplification of alleles I and D resulted in 490 bp and 190 bp products, respectively. ACE genotype DD was present in 47% of patients with CAD as compared to 30% in the general population (p = 0.0002, Odds ratio 2.7). The frequency of allele D was 0.68 in patients with CAD and 0.55 in general population, respectively (p < 0.0001). Genotype DD was associated with CAD only in males (54% vs. 30%, p = 0.0001, Odds ratio 2.0), but not in female patients. There was no association between the frequency of ACE genotype DD and the prior history of myocardial infarction, or the extent of CAD. The frequency of ACE genotype DD was the highest among patients with restenosis following angioplasty (55%), however, the difference was not significantly changed as compared to those without restenosis (40%).

CONCLUSIONS

ACE genotype DD is more common in patients with CAD as compared to the general population, indicating that genotype DD is a genetic risk factor for CAD.

摘要

背景

冠状动脉疾病（CAD）是一种多基因疾病，其表型表现是多种环境因素与潜在遗传背景相互作用的结果。包括血管紧张素I转换酶（ACE）基因在内的许多基因都与CAD的发病机制有关。ACE可影响低密度脂蛋白的氧化、内皮细胞功能以及平滑肌细胞的迁移和增殖，而这些都是动脉粥样硬化的重要组成部分。ACE基因的一种变体，即基因型DD，与较高的血浆ACE水平以及心肌梗死和心肌病风险增加相关。在本研究中，我们试图确定接受冠状动脉血管成形术的CAD患者中ACE基因型的分布以及等位基因D的频率。

方法

采用先前发表的方案，通过聚合酶链反应（PCR）对182例接受冠状动脉血管成形术的白人患者和338例明显健康的白人个体的DNA进行多态性区域扩增。

结果

等位基因I和D的PCR扩增分别产生490bp和190bp的产物。CAD患者中ACE基因型DD的比例为47%，而普通人群中为30%（p = 0.0002，优势比2.7）。CAD患者中等位基因D的频率分别为0.68，普通人群中为0.55（p < 0.0001）。基因型DD仅在男性CAD患者中相关（54%对30%，p = 0.0001，优势比2.0），而在女性患者中无相关性。ACE基因型DD的频率与心肌梗死病史或CAD的严重程度之间无关联。血管成形术后再狭窄患者中ACE基因型DD的频率最高（55%），然而，与无再狭窄患者（40%）相比，差异无显著变化。