Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves
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.
CTSNet classification
35.1
35.2
Abbreviations and Acronyms
AAA
abdominal aortic aneurysm
ACE
angiotensin-converting enzyme
BAV
bicuspid aortic valve
CAD
coronary artery disease
CI
confidence interval
I/D
insertion/deletion
OR
odds ratio
RAS
renin-angiotensin system
TAA
thoracic aortic aneurysm
TAV
tricuspid aortic valve
Cited by (0)
This research was partially funded by Ente Cassa di Risparmio di Firenze.
Disclosures: Authors have nothing to disclose with regard to commercial support.