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


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.
Fatini
C
C
Department of Medical and Surgical Critical Care, University of Florence, Thrombosis Center, Azienda Ospedaliera Careggi, Florence, Italy.
Gensini
F
F
Sticchi
E
E
Battaglini
B
B
Prisco
D
D
Fedi
S
S
Brunelli
T
T
Marcucci
R
R
Conti
A A
AA
Gensini
G F
GF
Abbate
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003545:Cysteine / Q000097:blood; D005165:Factor V / Q000235:genetics; D005260:Female; D005838:Genotype; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D007703:Peptidyl-Dipeptidase A; D003545:Cysteine