Celermajer D S, Sorensen K E, Barley J, Jeffrey S, Carter N, Deanfield J
Cardiothoracic Unit, Hospital for Sick Children, London, UK.
Atherosclerosis. 1994 Nov;111(1):121-6. doi: 10.1016/0021-9150(94)90197-x.
The DD genotype is a polymorphism of the angiotensin-converting enzyme (ACE) gene, and is associated with a significantly increased risk of myocardial infarction. As endothelial dysfunction is an important event in both early atherogenesis and late atherosclerosis, we hypothesised that the adverse effect associated with the ACE/DD genotype might be mediated via endothelial damage. Using high resolution ultrasound, we studied the brachial arteries of 184 subjects aged 15-73 (mean 38 +/- 14) years, who were all normotensive, non-diabetic lifelong non-smokers. Arterial diameter was measured at rest, during reactive hyperaemia (with flow increase causing endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN, an endothelium-independent vasodilator). The ACE genotype was determined in each case by DNA amplification; 49/184(27%) had DD, 89 (48%) had ID and 46 (25%) had II genotype. Flow-mediated dilation (FMD) was 8.5% +/- 3.9% in the DD, 7.8% +/- 4.1% in the ID and 7.8% +/- 4.1% in the II subjects (P = NS). GTN-induced dilation was also similar in the 3 groups. On multivariate analysis, endothelium-dependent dilation was inversely related to age (r = -0.33, P < 0.001), vessel size (r = -0.41, P < 0.001) but not ACE genotype (r = 0.002, P = 0.97). The ACE genotype is unrelated to endothelium-dependent dilation in the systemic arteries of clinically well adults. This suggests that the risk associated with this polymorphism may be mediated by other mechanisms.
DD基因型是血管紧张素转换酶（ACE）基因的一种多态性，与心肌梗死风险显著增加相关。由于内皮功能障碍在早期动脉粥样硬化形成和晚期动脉粥样硬化过程中均是重要事件，我们推测与ACE/DD基因型相关的不良影响可能是通过内皮损伤介导的。我们使用高分辨率超声研究了184名年龄在15 - 73岁（平均38±14岁）的受试者肱动脉情况，这些受试者均为血压正常、非糖尿病、终身不吸烟者。在静息状态、反应性充血期间（血流增加导致内皮依赖性扩张）以及舌下含服硝酸甘油后（GTN，一种非内皮依赖性血管扩张剂）测量动脉直径。通过DNA扩增确定每种情况下的ACE基因型；184例中有49例（27%）为DD基因型，89例（48%）为ID基因型，46例（25%）为II基因型。DD基因型受试者的血流介导的扩张（FMD）为8.5%±3.9%，ID基因型受试者为7.8%±4.1%，II基因型受试者为7.8%±4.1%（P =无显著性差异）。3组中GTN诱导的扩张也相似。多因素分析显示，内皮依赖性扩张与年龄呈负相关（r = -0.33，P < 0.001），与血管大小呈负相关（r = -0.41，P < 0.001），但与ACE基因型无关（r = 0.002，P = 0.97）。在临床健康的成年人全身动脉中，ACE基因型与内皮依赖性扩张无关。这表明与这种多态性相关的风险可能是由其他机制介导的。
