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Thromb Haemost 1998; 80(06): 869-873
DOI: 10.1055/s-0037-1615379
Letters to the Editor
Schattauer GmbH

Deletion Polymorphism in the Angiotensin-converting Enzyme Gene as a Thrombophilic Risk Factor after Hip Arthroplasty

Claire S. Philipp
1   Divisions of Hematology and Orthopedic Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey
,
Anne Dilley
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
,
Parvin Saidi
1   Divisions of Hematology and Orthopedic Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey
,
Bruce Evatt
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
,
Harland Austin
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
,
Joseph Zawadsky
1   Divisions of Hematology and Orthopedic Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey
,
David Harwood
1   Divisions of Hematology and Orthopedic Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey
,
Dorothy Ellingsen
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
,
Elizabeth Barnhart
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
,
Donald J. Phillips
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
,
William Craig Hooper
2   Hematologic Diseases Branch, NCID, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
› Author Affiliations
Further Information

Publication History

Received 08 May 1998

Accepted after revision 04 August 1998

Publication Date:
07 December 2017 (online)

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Summary

Despite thromboprophylaxis, deep vein thrombosis is a common complication of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n = 43) was lowest in persons homozygous for the I allele (18.9 ± 7.95 U/l), intermediate in patients with the ID genotype (31.6 ± 10.8 U/l) and highest in subjects homozygous for the D allele (44.0 ± 7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n = 25) than among controls (29.4 U/l, n = 43) but this difference was not statistically significant. Neither the Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.

 

  • References

  • 1 Claggett GP, Anderson FA, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism.. Chest 1995; 108: 312S-34S.
    CrossrefPubMedGoogle Scholar
  • 2 Turpie AGG, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, Andrew M, Hull RD, Gent M. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery.. N Engl J Med 1986; 315: 925-9.
    CrossrefPubMedGoogle Scholar
  • 3 Hull RC, Raskob GE, Pineo GF. et al. A comparison of subcutaneous low-molecular weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation.. N Engl J Med 1993; 329: 1370-6.
    CrossrefPubMedGoogle Scholar
  • 4 Bergvist D, Benoni G, Bjorgell O, Fredin H, Hedlundh U, Nicolas S, Nilsson P, Nylander G. Low molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement.. N Engl J Med 1996; 335: 696-700.
    CrossrefPubMedGoogle Scholar
  • 5 Lowe GDO. Prediction of postoperative deep-vein thrombosis.. Thromb Hemost 1997; 78: 47-52.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Rocha E, Alfaro MJ, Paramo JA, Canadell JM. Preoperative identification of patients at high risk of deep venous thrombosis despite prophylaxis in total hip replacement.. Thromb Hemost 1988; 59: 93-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Sharrock NE, Go G, Harpel PC, Ranawat CS, Sculco TP, Salvati EA. Thrombogenesis during total hip arthroplasty.. Clin Orth 1995; 319: 16-27.
    PubMedGoogle Scholar
  • 8 Rigat N, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P. Soubrier.. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.. J Clin Invest 1990; 86: 1343-6.
    CrossrefPubMedGoogle Scholar
  • 9 Samani N, Thompson JR, O’Toole L, Channer K, Woods KL. A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction.. Circulation 1996; 94: 708-12.
    CrossrefPubMedGoogle Scholar
  • 10 Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard J-M, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.. Nature 1992; 359: 641-4.
    CrossrefPubMedGoogle Scholar
  • 11 Mattu RK, Needham EW, Galton DJ, Frangos E, Clark AJ, Caulfield M. A DNA variant at the angiotensin-converting enzyme gene locus associates with coronary artery disease in the Caerphilly Heart Study.. Circulation 1995; 91: 270-4.
    CrossrefPubMedGoogle Scholar
  • 12 Ludwig E, Corneli PS, Anderson JL, Marshall HW, Laoulel JM, Ward RH. Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis.. Circulation 1995; 91: 2120-4.
    CrossrefPubMedGoogle Scholar
  • 13 Agerholm-Larsen B, Nordestghaard BG, Steffensen R, Sorensen TI, Jensen G, Tybjaerg-Hansen A. ACE gene polymorphism: ischemic heart disease and longevity in 10150 individuals. A case-referent and retrospective cohort study based on the Copenhagen City Heart Study.. Circulation 1997; 95: 2358-67.
    CrossrefPubMedGoogle Scholar
  • 14 Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.. N Eng J Med 1995; 332: 706-11.
    CrossrefPubMedGoogle Scholar
  • 15 Dzau VJ. Cell biology and genetics of angiotensin in cardiovascular disease.. J Hyper 1994; 12 (Suppl. 04) S3-S10.
    PubMedGoogle Scholar
  • 16 Bertina RM, Koelman BPC, Koster T, Rosendaal FR, Duven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C.. Nature 1994; 369: 64-7.
    CrossrefPubMedGoogle Scholar
  • 17 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.. Proc Natl Acad Sci USA 1993; 90: 1004-8.
    CrossrefPubMedGoogle Scholar
  • 18 Sun X, Evatt B, Griffin JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia.. Blood 1994; 83: 3120-5.
    PubMedGoogle Scholar
  • 19 Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kliutman LA, van den Heuvel P. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.. Nat Genet 1995; 10: 111-3.
    CrossrefPubMedGoogle Scholar
  • 20 Den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH, Vandenbrouckes P, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis.. N Engl J Med 1996; 334: 759-62.
    CrossrefPubMedGoogle Scholar
  • 21 Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/ deletion polymorphism of the human angiotensin I converting enzyme gene (DCPI).. Nucleic Acid Res 1992; 20: 1433.
    PubMedGoogle Scholar
  • 22 Dilley A, Austin H, Hooper WC, Latty C, Ribeiro MJ, Wenger NK, Silva V, Rawlins P, Evatt B. Relation of three genetic traits to venous thrombosis in an African-American Population.. Am J Epidemiol 1998; 147: 1-6.
    CrossrefPubMedGoogle Scholar
  • 23 Hooper WC, Dilley A, Ribeiro MJ, Benson J, Austin H, Silva V, Rawlins P, Wenger NK, Evatt BL. A racial difference in the prevelance of the Arg506>Gln mutation.. Thromb Res 1996; 81: 577-81.
    CrossrefPubMedGoogle Scholar
  • 24 Austin H, Hooper WC, Dilley A, Drews C, Renshow M, Ellingsen D, Evatt B. The prevelance of two genetic traits related to venous thrombosis in whites and African-Americans.. Thromb Res 1997; 86: 409-15.
    CrossrefPubMedGoogle Scholar
  • 25 Martin D, Austin H. An efficient program for computing conditional maximum likelihood estimates and exact confidence limits for a common odds ratio.. Epidemiology 1991; 2: 359-62.
    CrossrefPubMedGoogle Scholar
  • 26 Snedecor W, Cochran WG. Statistical Methods.. Eight Edition. Ames, IA, Iowa State University,; 1989
    PubMedGoogle Scholar
  • 27 Winkelmann BR, Nauck M, Klein B, Russ AP, Bohm BO, Siekmeier R, Ihnken K, Verho M, Grob W, Marz W. 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: 19-25.
    CrossrefPubMedGoogle Scholar
  • 28 Rakugi H, Kim DK, Krieger JE, Wang DS, Dzau VJ. Induction of angiotensin converting enzyme in the neointima after vascular injury: possible role in restenosis.. J Clin Invest 1994; 93: 339-46.
    CrossrefPubMedGoogle Scholar
  • 29 Ryan DH, Crowther MA, Ginsberg JS, Francis CW. Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.. Ann Intern Med 1998; 128: 270-6.
    CrossrefPubMedGoogle Scholar
  • 30 Svensson PJ, Benoni G, Fredin H, Bjorgell O, Nilsson P, Hedlund U, Ny-lander G, Bergqvist D, Dahlbäck B. Female gender and resistance to ac tivated protein C (FV:Q506) as potential risk factors for thrombosis after elective hip arthroplasty.. Thromb Hemost 1997; 77: 993-6.
    PubMedGoogle Scholar