title: Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves.
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.
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Foffa
authors.forename: Michele
authors.initials: M
authors.lastname: Murzi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mariani
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mazzone
authors.forename: Mattia
authors.initials: M
authors.lastname: Glauber
authors.forename: Lamia
authors.initials: L
authors.lastname: Ait Ali
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D000328:Adult; D000368:Aged; D017545:Aortic Aneurysm, Thoracic / Q000453:epidemiology / Q000235:genetics*; D001021:Aortic Valve / Q000002:abnormalities*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D007703:Peptidyl-Dipeptidase A