title: 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.
  
  
  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.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Thrombosis Center, Azienda Ospedaliera Careggi, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fatini
authors.forename: F
authors.initials: F
authors.lastname: Gensini
authors.forename: E
authors.initials: E
authors.lastname: Sticchi
authors.forename: B
authors.initials: B
authors.lastname: Battaglini
authors.forename: D
authors.initials: D
authors.lastname: Prisco
authors.forename: S
authors.initials: S
authors.lastname: Fedi
authors.forename: T
authors.initials: T
authors.lastname: Brunelli
authors.forename: R
authors.initials: R
authors.lastname: Marcucci
authors.forename: A A
authors.initials: AA
authors.lastname: Conti
authors.forename: G F
authors.initials: GF
authors.lastname: Gensini
authors.forename: R
authors.initials: R
authors.lastname: Abbate
mesh_terms: 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*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D007703:Peptidyl-Dipeptidase A; D003545:Cysteine