Angiotensin converting enzyme (ACE) DD genotype: relationship with venous thrombosis

Abstract

Venous thromboembolism is a common multifactorial disease associated with acquired and inherited predisposing factors. Several polymorphisms, e.g. factor V Leiden, factor II G20210A and deficiency of antithrombin, protein C and protein S, have been associated with venous thromboembolism. Angiotensin converting-enzyme affects hemostasis by decreasing fibrinolysis. Angiotensin converting-enzyme gene polymorphism, a 287 pb insertion/deletion at introns 16, is related to variations in enzyme serum levels. The DD genotype has been associated with increased risk for venous thrombosis. This study examined the frequency of the angiotensin converting-enzyme alleles I and D and their association with venous thrombosis in a group of individuals from the south of Brazil. Seventy-one patients with deep venous thrombosis and/or pulmonary thromboembolism and 71 healthy individuals were analysed in a case-control study. The angiotensin converting-enzyme ID genotyping was performed by polymerase chain reaction. The frequencies of the D allele and DD genotype were, respectively, 51.4% and 22.5% for patients, and 64.7% and 45.0% for controls. The Odds Ratio for the dominant hypothesis (DD+ID versus II genotypes) was 0. 75 (CI 95%; 0.29-1.93) and the Odds Ratio for recessive hypothesis (DD versus ID+II) was 0.35 (CI 95%; 0.16-0.78). In conclusion, our results indicate a protective effect of the angiotensin converting-enzyme DD genotype on venous thromboembolism.

Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis

“…We did not investigate the mechanisms beyond this association. However, one possible explanation is that our patients with D allele probably have higher levels and activity of ACE, as previously reported in other studies [ 11 , 36 , 37 ]. Costerousse et al showed that T-lymphocyte levels of ACE were significantly higher in healthy subjects with D/D ACE polymorphism than in subjects with other genotypes [ 38 ].…”

ACE Gene I/D polymorphism and systemic arterial hypertension in different classes of hypertensive individuals

“…6 The D allele has been attributed with being responsible for an increase in vascular vasoconstriction, 16 due to increased ACE levels in the plasma and tissues of individuals with the D allele. 16,17 However, some studies have not found this association with the occurrence of coronary artery disease, 7 brain injury, 18 deep venous thrombosis and thromboembolism 19 and SAH, 5 leaving the biological significance of the I/D polymorphism of the ACE gene remaining an open question.…”

Association between deletion polymorphism of angiotensin converting enzyme gene and pulmonary hypertension in pulmonary thromboembolism

“…Studies performed on diverse ethnic groups implied that the deletion polymorphism of the ACE gene may be involved in venous thrombosis. [7,8,17] The ACE plays a significant role in vascular homeostasis through angiotensin II modeling and bradykinin inhibition. It has been reported that the ACE I/D genotype accounts for half of the phenotypic variance of serum ACE, and the ACE/ DD genotype has been associated with higher levels of serum ACE in the literature.…”

“…This gives rise to three genotypes: DD, ID, and II. [7,8] Pulmonary thromboembolism may lead to a number of complications with various severities. These include pneumonia, hemoptysis, pleural effusion, syncope, right-sided heart failure, and cardiogenic shock.…”