Role of Polymorphisms of Angiotensin Converting Enzyme Gene in Thoracic Ascending Aneurysm

OBJECTIVE: There are substantial data providing evidence that the renin- angiotensin system (RAS) is involved in the pathogenesis of abdominal aortic aneurysm. Limited data exist regarding the role of the RAS in thoracic ascending aneurysm (TAAs). In this study, the role of polymorphisms of one gene codifying a key member of RAS system were examined in cases affected by sporadic TAA and dissections. METHODS: Aortic specimens were obtained from 161 patients (127 men and 34 women, whose median age 63± 10.7 years) undergoing surgical repair of TAAs and 18 patients undergoing surgical repair for Stanford type A aortic dissection (TAD). A control group of 128 subjects (61 men and 67 woman, mean age: 61.1 ± 5.8 years) was also enrolled. Histopathological and immunohistochemical analyses were performed using adequate tissue specimens, appropriate techniques and criteria. Furthermore, genotyping of common and functional single nucleotide genetic polymorphisms (SNP)s of Angiotensin Converting Enzyme (ACE) gene was performed. RESULTS: Three phenotypes of TAAs, were identified in case aorta samples: phenotype I (normal wall); phenotype II (moderate wall thickness); phenotype III (thin and weak wall). Same medial lesions were observed in TAA phenotype III and TAD: elevated cystic medial degeneration, without substitutive fibrosis, with plurifocal medial apoptosis and elevated collagenase concentrations. In addition, the genotyping revealed a significant association of the D/I ACE SNP with the risk of sporadic TAA and TAD (OR= 5.6 (2.1-8.8) p=0.001 and OR=3.1 (1.1-6.7) p=0.001, respectively). A significant association was also detected between this SNP and phenotype III (p=0.01). The weight of the biological effect of this SNO is to determine high levels of ACE.