ACE DD genotype: an independent predisposition factor to venous thromboembolism.

Abstract Background The renin angiotensin system affects haemostasis through different mechanisms; data on the possible role of angiotensin-converting enzyme I/D polymorphism in the pathogenesis of deep venous thrombosis are conflicting, and no information is available regarding the A1166C polymorphism of the angiotensin type 1 receptor gene. In order to investigate this issue, angiotensin-converting enzyme and AT1R polymorphisms were genotyped in 336 consecutive venous thromboembolism patients and 378 controls. Materials and methods Haemostasis-related risk factors have been evaluated by routine tests. Factor V Leiden, Factor II (G20210A), angiotensin-converting enzyme (I/D), and angiotensin type 1 receptor (A1166C) polymorphisms have been identified by molecular analysis. Results We documented a significant association between angiotensin-converting enzyme DD genotype and venous thromboembolism (OR = 2·19 95%CI 1·51–3·17 adjusted for acquired and haemostasis-related risk factors, P < 0·0001); in patients with haemostasis-related risk factors, angiotensin-converting enzyme DD genotype modified the risk of venous thromboembolism in hyperhomocysteinaemic and Factor V Leiden patients and was associated with the risk of recurrent venous thromboembolism (OR = 1·83 95%CI 1·06–3·17 P = 0·03). In patients without haemostasis-related risk factors the angiotensin-converting enzyme DD genotype was still an independent predictor of venous thromboembolism (OR = 3·29 95%CI 2·17–4·98 adjusted for acquired risk factors, P < 0·0001). No significant association between the angiotensin type 1 receptor CC genotype and venous thromboembolism was found. Conclusions This study shows that angiotensin-converting enzyme DD genotype represents a susceptibility marker of thrombosis in subjects apparently without predisposing factors and traditional thrombophilic alterations, and increases the risk of venous... [ABSTRACT FROM AUTHOR]