ACE DD genotype: an independent predisposition factor to venous thromboembolism

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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 thromboembolism in subjects in whom a thrombogenic condition occurs. Moreover, angiotensin‐converting enzyme DD genotype may be considered a new predisposing factor to venous thromboembolism recurrence.

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