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Thromb Haemost 2003; 90(05): 829-834
DOI: 10.1160/TH03-03-0170
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The ACE D/D genotype is protective against the development of idiopathic deep vein thrombosis and pulmonary embolism

Philip S. Wells
1   Departments of Medicine
2   Epidemiology and Community Medicine
5   Ottawa Health Research Institute, Canada
,
Marc A. Rodger
1   Departments of Medicine
2   Epidemiology and Community Medicine
5   Ottawa Health Research Institute, Canada
,
Melissa A. Forgie
1   Departments of Medicine
2   Epidemiology and Community Medicine
5   Ottawa Health Research Institute, Canada
,
Nicole J. Langlois
5   Ottawa Health Research Institute, Canada
,
Linlea Armstrong
6   Children’s Hospital of Eastern Ontario, Canada
,
Nancy L. Carson
3   Pediatrics, Microbiology and Immunology, University of Ottawa, Canada
4   Biochemistry, Microbiology and Immunology, University of Ottawa, Canada
6   Children’s Hospital of Eastern Ontario, Canada
,
James Jaffey
5   Ottawa Health Research Institute, Canada
› Author AffiliationsGrant support: Heart and Stroke Foundation of Ontario, Grant Number NA4507 Dr. Wells is a Canada Research Chair. Dr. Rodger is a recipient of the Maureen Andrew New Investigator Award (#5078) from the Heart and Stroke Foundation of Canada. N. Langlois is funded through a Premier’s Research Excellence Award, granted to Dr. Wells. Department and institution where work was conducted: Department of Medicine, Ottawa Hospital: General and Civic Campuses, Canada Molecular Genetics Diagnostic Lab, Children’s Hospital of Eastern Ontario, Canada
Further Information

Publication History

Received 20 March 2003

Accepted after revision 03 July 2003

Publication Date:
05 December 2017 (online)

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Summary

The deletion/deletion (D/D) genotype of the angiotensin converting enzyme (ACE) has been purported to be a risk for postoperative thrombosis. This D/D genotype has not been evaluated as a risk factor for idiopathic venous thromboembolism (VTE).

The primary objective of the present study was to determine whether the D/D genotype of ACE is independently associated with the occurrence of idiopathic venous thromboembolic disease.

We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic VTE. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. Patients were tested for the ACE I/D polymorphism in addition to factor V Leiden, prothrombin G20210A, and factor VIII levels.

Three hundred cases and 300 controls were enrolled; 97% were Caucasian. There were 148 females and 152 males in each group with a mean age of 56.21 years (SD=15.33). The ACE D/D genotype was present in 25.3% of cases and 32.4% of controls for an adjusted odds ratio of 0.66 (95% CI = 0.433 to 0.997). We can conclude that the ACE D/D genotype is protective against idiopathic venous thromboembolism.

Keywords

ACE - angiotensin converting enzyme - venous thromboembolism - deep vein thrombosis - pulmonary embolism
 

  • References

  • 1 Bauer KA. The thrombophilias: well-defined risk factors with uncertain therapeutic implications. Ann Intern Med 2001; 135 (05) 367-73.
    CrossrefPubMedGoogle Scholar
  • 2 Winkelmann BR, Nauck M, Klein B. et al Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease. Ann Intern Med 1996; 125 (01) 19-25.
    CrossrefPubMedGoogle Scholar
  • 3 Pawlak R, Chabielska E, Golatowski J. et al Nitric oxide and prostacyclin are involved in antithrombotic action of captopril in venous thrombosis in rats. Thromb Haemost 1998; 79: 1208-12.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Moulder JE, Fish BL, Cohen EP. et al Angiotensin II receptor antagonists in the prevention of radiation nephropathy. Radiat Res 1996; 146 (01) 106-10.
    CrossrefPubMedGoogle Scholar
  • 5 Dilley A, Austin H, Hooper WC. et al Relation of three genetic traits to venous thrombosis in an African-American population. Am J Epidemiol 1998; 147 (01) 30-5.
    CrossrefPubMedGoogle Scholar
  • 6 Gonzalez Ordonez AJ, Fernandez Carreira JM, Medina Rodriguez JM. et al Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene. Blood Coagul Fibrinolysis 2000; 11 (05) 485-90.
    CrossrefPubMedGoogle Scholar
  • 7 Lu Y, Hui R, Zhao Y. Insertion/deletion poly-morphism of the angiotensin I converting enzyme gene and pulmonary thromboembolism in Chinese population. Zhonghua Jie He He Hu Xi Za Zhi 2001; 24 (05) 265-8.
    PubMedGoogle Scholar
  • 8 Philipp CS, Dilley A, Saidi P. et al Deletion polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty. Thromb Haemost 1998; 80: 869-73.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Jackson A, Brown K, Langdown J. et al Effect of the angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism. Br J Haematol 2000; 111 (02) 562-4.
    CrossrefPubMedGoogle Scholar
  • 10 Couturaud F, Kearon C. Treatment of deep vein thrombosis. Sem Vasc Med 2002; 1 (01) 43-54.
    PubMedGoogle Scholar
  • 11 Koster T, Blann AD, Briet E. et al Role of clotting factor VIII an effect of von Willebrand factor on occurrence of DVT. Lancet 1995; 345: 152-5.
    CrossrefPubMedGoogle Scholar
  • 12 Rosendaal FR. Venous thrombosis: A multi-causal disease. Lancet 1999; 353: 1167-73.
    CrossrefPubMedGoogle Scholar
  • 13 Kamphuisen PW, Eikenboom JCJ, Vos HL. et al Increased levels of factor VIII and fibrino-gen in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost 1999; 81: 680-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Bertina RM, Rosendaal FR. Venous thrombosis – The interaction of genes and the environment. N Engl J Med 1998; 338 (25) 1840-1.
    CrossrefPubMedGoogle Scholar
  • 15 Frezzato M, Tosetto A, Rodeghiero F. Validated questionnaire for the identification of previous personal or familial venous thromboembolism. Am J of Epidemiol 1996; 143 (12) 1257-65.
    CrossrefPubMedGoogle Scholar
  • 16 Donnelly JG, Rock GA. Genetic determinants of heritable venous thrombosis: genotyping methods for factor V(Leiden)A1691G, methylenetetrahydrofolate reductase C677T, pro-thrombin G20210A mutation, and algorithms for venous thrombosis investigations. Clin Biochem 1999; 32 (03) 223-8.
    CrossrefPubMedGoogle Scholar
  • 17 Rigat B, Hubert C, Corvol P. et al PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 1992; 20 (06) 1433
    PubMedGoogle Scholar
  • 18 Shanmugam V, Sell KW, Saha BK. Mistyping ACE heterozygotes. PCR Methods Appl 1993; 3 (02) 120-1.
    CrossrefPubMedGoogle Scholar
  • 19 Ryan DH, Crowther MA, Ginsberg JS. et al Relation of Factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery. Ann Intern Med 1998; 128 (04) 270-6.
    CrossrefPubMedGoogle Scholar
  • 20 Kearon C, Gent M, Hirsh J. et al Extended anticoagulation compared to placebo after three months of therapy for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340 (12) 901-7.
    CrossrefPubMedGoogle Scholar
  • 21 Stewart GJ, Lachman JW, Alburger PD. et al Intraoperative venous dilation and subsequent development of deep vein thrombosis in patients undergoing total hip or knee replacement. Ultrasound Med Biol 1990; 16 (02) 133-40.
    CrossrefPubMedGoogle Scholar
  • 22 Poort SW, Rosendaal FR, Reitsma PH. et al A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88 (10) 3698-703.
    PubMedGoogle Scholar
  • 23 Bertina RM, Koeleman BP, Koster T. et al Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369 6475 64-7.
    CrossrefPubMedGoogle Scholar
  • 24 Emmerich J, Rosendaal FR, Cattaneo M. et al Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism–pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 2001; 86 (03) 809-16.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Kearon C, Gent M, Hirsh J. et al A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340 (12) 901-7.
    CrossrefPubMedGoogle Scholar
  • 26 Agnelli G, Prandoni P, Santamaria MG. et al Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med 2001; 345 (03) 165-9.
    CrossrefPubMedGoogle Scholar
  • 27 Ridker PM, Glynn RJ, Miletich JP. et al Age-specific incidence rates of venous thromboembolism among heterozygous carriers of Factor V Leiden mutation. Ann Intern Med 1997; 126 (07) 528-31.
    CrossrefPubMedGoogle Scholar
  • 28 Zoller B, Berntsdotter A, Garcia de Frutos P. et al Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85 (12) 3518-23.
    PubMedGoogle Scholar
  • 29 van Boven HH, Vandenbroucke JP, Westendorp RGJ. et al Mortality and causes of death in inherited antithrombin deficiency. Thromb Haemost 1997; 77 (03) 452-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Makris M, Preston FE, Beauchamp NJ. et al Co-Inheritance of the 20210A allele of the prothrombin gene increases the risk of thrombosis in subjects with familial thrombophilia. Thromb Haemost 1997; 78: 1426-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Rothman KJ, Greenland S. Case-control studies. In: Rothman KJ, Greenland S, editors. Modern Epidemiology. Philadelphia, PA: Lippincott Williams & Wilkins; 1998: 93-114.
    Google Scholar