ACE DD Genotype: A Predisposing Factor to Abdominal Aortic Aneurysm

Abstract number: P1720

Fatini¹ C, Sticchi¹ E, Lari¹ B, Bolli¹ P, Sofi¹ F, Pratesi² G, Pulli² R, Pratesi² C, Abbate¹ R, Gensini¹ GF

¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ¹¹Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ²²Department of Medical and Surgical Critical Care, Unit of Vascular Surgery, University of Florence, Italy

Genetic and environmental components contribute to the aetiology and progression of aortic aneurysms. To date, ACE I/D and AT1R A1166C polymorphisms in genes encoding for Renin Angiotensin System (RAS) components have been demonstrated to be associated with atherosclerotic lesions and ACE D allele has been related to angiotensin II plasma levels. Experimental studies demonstrated that angiotensin II infusion produced abdominal aortic aneurysm (AAA). In humans few data are available regarding the role of RAS in aneurysm formation. In order to determine the role of these two polymorphisms in the development of AAA, we investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50–83), undergone to AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: P= 0.0002 and P < 0.0001, respectively and AT1R A1166C: P= 0.6 and P= 0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID + II = 1.9 95% CI 1.3–2.9 P < 0.0001). The OR for the predisposition to AAA varied from 1.76 (P= 0.019) in ID heterozygotes to 2.86 (P < 0.0001) in DD homozygotes, with a dose dependent effect. From the multivariate analysis adjusted for age, sex, and traditional vascular risk factors, ACE DD genotype was found to be independently related to the disease (OR DD vs. ID + II = 2 95% CI 1.2–3.3 P= 0.007). Our findings document a role for ACE gene I/D polymorphism in the pathogenesis of a complex disease, such as AAA.