血管紧张素转换酶插入/缺失多态性是二叶式或三叶式主动脉瓣患者胸主动脉瘤的危险因素。

Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves.

机构信息

CNR Institute of Clinical Physiology, Pisa, Italy.

出版信息

J Thorac Cardiovasc Surg. 2012 Aug;144(2):390-5. doi: 10.1016/j.jtcvs.2011.12.038. Epub 2012 Jan 14.

DOI:10.1016/j.jtcvs.2011.12.038

PMID:22245237

Abstract

OBJECTIVE

The angiotensin-converting enzyme (ACE) is highly expressed in the aneurysmal vascular wall, in both animal models and human disease. Genetic variations in ACE could be crucial in determining the risk of thoracic aortic aneurysm (TAA). The aim of the present study was to examine the role of ACE insertion/deletion polymorphism on the risk of TAA in patients with bicuspid aortic valves or tricuspid aortic valves.

METHODS

We enrolled 216 patients (158 men; age, 58.9±14.9 years) with TAA, associated with bicuspid aortic valves (n=105) and tricuspid aortic valves (n=111) compared with 312 patients (252 men; age, 54.6±11.0 years) with angiographically proven coronary artery disease and 300 healthy controls (91 men; age, 40.4±10.5 years).

RESULTS

The genotype distribution of ACE insertion/deletion was significantly different between the patients with TAA compared with both the control group (P=.0005) and the coronary artery disease group (P=.03). The genotypes were not different between the control group and the coronary artery disease group (P=.3). Compared with the controls, both the bicuspid aortic valve patients (P=.0008) and tricuspid aortic valve patients (P<.0001) had a greater frequency of allele D. The aortic diameters were significantly different among the three genotypes (48.3±6.6, 45.3±8.9, 39.9±8.7 for the DD, DI, and II genotypes, respectively; P=.0002). A synergistic effect between the ACE D allele and hypertension was found for both an increased aortic diameter (P=.003) and the risk of TAA (P<.001). On multivariate logistic regression analysis, D allele (odds ratio, 3.0; 95% confidence interval, 1.1-8.1; P=.03) was a significant predictor of TAA.

CONCLUSIONS

ACE insertion/deletion polymorphism represents a genetic biomarker for TAA. These findings could have a significant effect on both the early detection and effective pharmacologic treatment of aortic disease.

摘要

目的

血管紧张素转换酶（ACE）在动脉瘤血管壁中高度表达，在动物模型和人类疾病中均如此。ACE 的基因变异可能在决定胸主动脉瘤（TAA）的风险方面起着至关重要的作用。本研究旨在研究 ACE 插入/缺失多态性在二叶式主动脉瓣和三叶式主动脉瓣患者 TAA 风险中的作用。

方法

我们纳入了 216 名 TAA 患者（158 名男性；年龄 58.9±14.9 岁），其中 105 名患者伴二叶式主动脉瓣，111 名患者伴三叶式主动脉瓣，并与 312 名经血管造影证实的冠心病患者（252 名男性；年龄 54.6±11.0 岁）和 300 名健康对照者（91 名男性；年龄 40.4±10.5 岁）进行比较。

结果

与对照组（P=.0005）和冠心病组（P=.03）相比，TAA 患者 ACE 插入/缺失的基因型分布存在显著差异。对照组和冠心病组之间的基因型无差异（P=.3）。与对照组相比，二叶式主动脉瓣患者（P=.0008）和三叶式主动脉瓣患者（P<.0001）的 D 等位基因频率更高。三种基因型之间的主动脉直径存在显著差异（DD、DI 和 II 基因型分别为 48.3±6.6、45.3±8.9 和 39.9±8.7；P=.0002）。ACE D 等位基因与高血压之间存在协同作用，可导致主动脉直径增大（P=.003）和 TAA 风险增加（P<.001）。多变量 logistic 回归分析显示，D 等位基因（比值比，3.0；95%置信区间，1.1-8.1；P=.03）是 TAA 的显著预测因子。