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199406, —анкт-ѕетербург, ул.√аванска€, д. 49, корп.2

ISSN 1999-6314

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Vol. 14, Art. 66 (pp. 819-844)    |    2013       

Genetic polymorphism of soluble haemostatic factors in the pathogenesis of venous thromboembolism
Demyanenko A.V.1, Kapustin S.I.2, Soroka V.V.1, Chechulov P.V.1

1Emergency research institute named after I.I. Dzhanelidze, St. Petersburg
2Russian research institute of hematology and transfusiology, St. Petersburg

Brief summary

The frequency of occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) is about 1 in 1000 annually. Venous thromboembolism (VTE) is a multifactor disease with the underlying genetic defects so called thrombophilia. Based on the recent research, genetic factors with increased risk of VTE development include deficiencies of natural anticoagulants (protein C, protein S, antithrombin III) and mutations in the factor V (FV Leiden) and prothrombin (FII G20210A) genes. Notably, the careful analysis of patients with VTE and their relatives couldnТt find these mutations in more than 50% of family cases. This fact reflects the presence of other thrombophilic conditions underlying a large proportion of VTE episodes. The main goal of this article is to analyze and represent the information from different literary sources about the role of genetic polymorphism of the soluble haemostatic factors in VTE pathogenesis. We provide a systematic review of more than 50 original articles and meta-analyses cited in Medline and PubMed that focus on this problem.

Key words

venous thrombosis, risk factor, inherited thrombophilia

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Reference list

1. Virchow R LK. Translation in Matzdorff AC, Bell WR, trans, editor. Thrombosis and†embolie (1846Ц1856) // Canton, MA: Science History Publications. Ц 1998. / Originally published in German as УThrombose und Embolie. Gefdssentzndung und septische Infektion,Ф Gesammelte Abhandlungen zur wissenschaftlichen Medicin. Frankfurt am Main: Von Meidinger & Sohn. Ц 1856. Ц P. 219Ц732.

2. Heit JA. Venous thromboembolism epidemiology: implications for prevention and management // Semin Thromb Hemost. Ц 2002. Ц 28 (Suppl 2). Ц P. 3Ц13.

3. Kirienko A.I., Mishnev O.L., Ciciashvili M.Sh., V.F. Agafonov V.F. Problema posleoperacionnih venoznih tromboembolicheskih oslojnenii v hiryrgicheskoi praktike // Angiologiya i sosydistaya hiryrgiya, 2003. t.є 1.-S.61-65

4. Dahlbdck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders // Blood. Ц 2008. Ц Vol. 112 (1). Ц P. 19Ц27

5. Wakefield TW, Myers DD, Henke PK. Mechanisms of Venous Thrombosis and Resolution // Arteriosclerosis, Thrombosis, and Vascular Biology. 2008. Ц Vol. 28. Ц P. 387.

6. Virchow RLK. Phlogose und thrombose im GefdYasystem // Gesammelte Abhandlung zur Wissenchaftlichen Medizin. Franksfurt, Germany: Staatsdruckerei. Ц 1856.

7. Lund FL, Diener L, Ericsson JLE. Postmortem intraosseous phlebography as an aid in studies of venous thromboembolism: with application on a geriatric clientele // Angiology. Ц 1969. Ц Vol. 20. Ц P. 155-176.

8. Brooks EG, Trotman W, Wadsworth MP, et al. Valves of the deep venous system: an overlooked risk factor // Blood. Ц 2009. Ц Vol. 114. Ц P. 1276Ц1279.

9. Egeberg O. Inherited antithrombin deficiency causing thrombophilia // Thromb Diath Haemorrh. Ц 1965. Ц Vol. 13. Ц P. 516Ц530.

10. Dahlback 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. Ц 1993. Ц Vol. 90. Ц P. 1004-8.

11. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3Т-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis // Blood. Ц 1996. Ц Vol. 88. Ц P. 3698-703.

12. Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D et al British Committee for Standards in Haematology. Clinical guidelines for testing for heritable thrombophilia // Br J Haematol. Ц 2010. Ц Vol. 149. Ц P. 209-20.

13. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothormbin (20210G>A) mutations in adults with a history of idiopathic VTE and their adult family members // Genet Med. Ц 2011. Ц Vol. 13. Ц P. 67-76.

14. Makacariya A.D., Bicadze V.O. Trombofilicheskie sostoyaniya v akysherskoi praktike. M: Russo 2001; 219Ч285.

15. De Stefano V., Rossi E. Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups // Thromb Haemost. Ц 2013. Ц Vol. 110(4). Ц R. 697-705.

16. Barkagan Z.S. Kliniko-patogeneticheskie varianti, nomenklatyra i osnovi diagnostiki gematogennih trombofilii. // Problemi gematologii. - 1996. - N 3. - S. 5-15.

17. Florell S.R., Rodgers G.M. Inherited thrombotic disorders: an update // American J. of Hematology. Ц 1997. Ц V.54. Ц R. 53-60.

18. Heit J.A. Thrombophilia: common questions on laboratory assessment and management // Hematology Am Soc Hematol Educ. Ц 2007. Ц Vol. 1. Ц P. 127Ц35.

19. Rosendaal FR, Reitsma P H Genetics of venous thrombosis // Journal of Thrombosis and Haemostasis. Ц 2009. Ц Vol. 7 (Suppl. 1). Ц P. 301Ц304.

20. Cooper PC, Coath F, Daly ME, Makris M. The phenotypic and genetic assessment of antithrombin deficiency // Int J Lab Hematol. Ц 2011. Ц Vol. 33(3). Ц P. 227-37.

21. Ishiguro K, Kojima T, Kadomatsu K, et al. Complete antithrombin deficiency in mice results in embryonic lethality // J Clin Invest. Ц 2000. Ц Vol. 106. Ц P. 873Ц878.

22. Goldenberg N.A, Manco - Johnson M.J. Protein C deficienc // Haemophilia. Ц 2008. Ц Vol. 14. Ц P. 1214Ц1221.

23. Rezende SM, Simmonds RE, Lane DA. Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex // Blood. Ц 2004. Ц Vol. 103. Ц P. 1192Ц201.

24. Wagh S., Anadure R., Dutta V., Sandhu M.S., Trehan R., Isolated protein S deficiency presenting as catastrophic systemic arterial and subsequently venous thrombosis // AMJ. Ц 2012. Ц Vol. 5 (8). Ц P. 424-428.

25. Cripe, L. D., Moore, K. D., Kane, W. H. Structure of the gene for human coagulation factor V // Biochemistry. Ц 1992. Ц Vol. 31. Ц P. 3777-3785.

26. Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis // N Engl J Med. Ц 1994. Ц Vol. 330. Ц P. 517Ц522.

27. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men // N Engl J Med. Ц 1995. Ц Vol. 332. Ц P. 912Ц917.

28. Lindqvist PG, Svensson PJ, Marsaal K, Grennert L, Luterkort M, Dahlback B. Activated protein C resistance (FV:Q506) and pregnancy // Thromb Haemost. Ц 1999. Ц Vol. 81. Ц P. 532Ц537.

29. van Stralen KJ, Doggen CJ, Bezemer ID, Pomp ER, Lisman T, Rosendaal FR. Mechanisms of the factor V Leiden paradox // Arterioscler Thromb Vasc Biol. Ц 2008. Ц Vol. 28. Ц P. 1872.

30. Huisman MV, Klok FA, Karami Djurabi R, Tormene D, Simioni P, Prandoni P. Factor V Leiden is associated with more distal location of deep vein thrombosis of the leg // J Thromb Haemost. Ц 2008. Ц Vol. 6. Ц P. 544Ц5.

31. Boyden EA. Segmental Anatomy of the Lungs: Study of the Patterns of the Segmental Bronchi and Related Pulmonary Vessels // New York, NY:McGraw-Hill. Ц 1955. Ц P. 23-32.

32. Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM, Crim MT, Bass EB. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review // JAMA. Ц 2009. Ц Vol. 301:2472Ц85.

33. Lancellotti, S., De Cristofaro, R. Congenital prothrombin deficiency // Semin. Thromb. Hemost. Ц 2009. Ц Vol. 35. Ц P. 367-381.

34. Degen, S. J. F., Schaefer, L. A., Jamison, C. S., Grant, S. G., Fitzgibbon, J. J., Pai, J.-A., Chapman, V. M., Elliott, R. W. Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2 // DNA Cell Biol. Ц 1990. Ц Vol. 9. Ц P. 487-498.

35. Rosendaal FR, Doggen CJ, Zivelin A, et al. Geographic distribution of the 20210 G to A prothrombin variant // Thromb Haemost. Ц 1998. Ц Vol. 79. Ц P. 706Ц708.

36. 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 casecontrol studies including 2310 cases and 3204 controls. Study group for pooled-analysis in venous thromboembolism // Thromb Haemost. Ц 2001. Ц Vol. 86. Ц P. 809-16.

37. Martinelli I, Battaglioli T, Tosetto A, Legnani C, Sottile L, Ghiotto R, Mannucci PM. Prothrombin A19911G polymorphism and the risk of venous thromboembolism // J Thromb Haemost. Ц 2006. Ц Vol. 4. Ц P. 2582Ц6.

38. Miles JS, Miletich JP, Goldhaber SZ, Hennekens CH, Ridker PM. G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism// J Am Coll Cardiol. Ц 2001. Ц Vol. 37. Ц P. 215Ц8.

39. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, Iotti M, Tormene D, Simioni P, Pagnan A. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients // Haematologica. Ц 2007. Ц Vol. 92. Ц P. 199Ц205.

40. Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events // JAMA. Ц 2005. Ц Vol. 293. Ц P. 2352Ц61.

41. Zybairov D.M. Molekylyarnie osnovi svertivaniya krovi i tromboobrazovaniya. Kazan: "Fen", 2000. Ц 364 s.

42. Standeven KF, Grant PJ, Carter AM, Scheiner T, Weisel JW, Ariens RA. Functional analysis of the fibrinogen Aalpha Thr312Ala polymorphism: effects on fibrin structure and function // Circulation. Ц 2003. Ц Vol. 107. Ц P. 2326Ц30.

43. Kain K, Blaxill JM, Catto AJ, Grant PJ, Carter AM. Increased fibrinogen levels among South Asians versus Whites in the United Kingdom are not explained by common polymorphisms // Am J Epidemiol. Ц 2002. Ц Vol. 156. Ц P. 174Ц9.

44. Gohil R, Peck G, Sharma P.The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000 controls // Thromb Haemost. Ц 2009. Ц Vol. 102(2). Ц P. 360-70.

45. Rasmussen-Torvik LJ, Cushman M, Tsai MY, Zhang Y, Heckbert SR, Rosamond WD, Folsom AR. The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study // Thromb Res. Ц 2007. Ц Vol. 121(1). Ц P. 1-7.

46. Carter AM, Catto AJ, Kohler HP, Ariens RA, Stickland MH, Grant PJ. alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism // Blood. Ц 2000. Ц Vol. 96. Ц P. 1177Ц9.†

47. van 't Hooft FM, von Bahr SJ, Silveira A, Iliadou A, Eriksson P, Hamsten A Two common, functional polymorphisms in the promoter region of the beta-fibrinogen gene contribute to regulation of plasma fibrinogen concentration // Arterioscler Thromb Vasc Biol. Ц 1999. Ц Vol. 19(12). Ц P. 3063-70.

48. Humphries SE, Luong LA, Montgomery HE, Day IN, Mohamed-Ali V, Yudkin JS. Gene-environment interaction in the determination of levels of plasma fibrinogen // Thromb Haemost. Ц 1999. Ц Vol. 82(2). Ц P. 818-25.

49. Chen XC, Xu MT, Zhou W, Han CL, Chen WQ. A meta-analysis of beta-fibrinogen gene-455G/A polymorphism and plasma fibrinogen level in Chinese cerebral infarction patients // Biomed Environ Sci. Ц 2007. Ц Vol. 20(5). Ц P. 366-72.

50. Tiedje V, Dunkler D, Ay C, Horvath B, Quehenberger P, Pabinger M, Zielinski C, Pabinger I, Mannhalter C.The role of fibrinogen plasma levels, the -455G>A fibrinogen and the factor XIII A subunit (FXIII-A) Val34Leu polymorphism in cancer-associated venous thrombosis // Thromb Haemost. Ц 2011. Ц Vol. 106(5). Ц P. 908-13

51. Kanaji T, Okamura T, Osaki K, Kuroiwa M, Shimoda K, Hamasaki N, Niho Y. A common genetic polymorphism (46 C to T substitution) in the 5'-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level // Blood. Ц 1998. Ц Vol.15; 91(6). Ц P. 2010-4.

52. Cochery-Nouvellon E, Mercier E, Lissalde-Lavigne G, Dauris JP, Quiri I, Dauzat M, Maris P, Gris JC Homozygosity for the C46T polymorphism of the F12 gene is a risk factor for venous thrombosis during the first pregnancy // J Thromb Haemost. Ц 2007. Ц Vol. 5(4). Ц P. 700-7.

53. Rasighaemi P, Kazemi A, Ala F, Jazebi M, Razmkhah F Association of FXII 5ТUTR 46C>T polymorphism with FXII activity and risk of thrombotic disease // Turkish Journal of Hematology. Ц 2010. Ц Vol. 27. Ц P. 15-19.

54. Bagoly Z, Koncz Z, Hbrsfalvi J, Muszbek L.Factor XIII, clot structure, thrombosis // Thromb Res. Ц 2012. Ц Vol. 129(3). Ц P. 382-7.

55. Lee IH, Chung SI, Lee SY. Effects of Val34Leu and Val35Leu polymorphism on the enzyme activity of the coagulation factor XIII-A // Exp Mol Med. Ц 2002. Ц Vol. 34(5). Ц P. 385-90.

56. Arilns RA, Philippou H, Nagaswami C, Weisel JW, Lane DA, Grant PJ. The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. // Blood. − 2000 Ц Vol. 96(3). Ц P. 988-95.

57. Red G, Tassies D, Espinosa G, Monteagudo J, Bovi A, Plaza J, Cervera R, Reverter JC. Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels // Thromb Haemost. Ц 2009. Ц Vol. 101(2). Ц P. 312-6.

58. Cushman M, Cornell A, Folsom AR, Wang L, Tsai MY, Polak J, Tang Z. Associations of the beta-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis // Thromb Res. Ц 2007. Ц Vol. 121(3). Ц P. 339-45.

59. Balogh I, Szfke G, Karpati L, et al. Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia // Blood. Ц 2000. Ц Vol. 96. Ц P. 2479Ц86.

60. Pastinen T,Perola M, Niini P,Terwilliger J, Salomaa V, Vartiainen E, Peltonen L, Syvdnen A.Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population // Hum Mol Genet. Ц 1998. Ц Vol. 7(9):1453-62.

61. Balta G, Altay C, Gurgey A.PAI-1 gene 4G/5G genotype: A risk factor for thrombosis in vessels of internal organs // Am J Hematol. Ц 2002. Ц Vol. 71(2):89-93.

62. Emeis JJ. The control of tPA and PAI-1 secretion from the vessel wall // Vasc Med Rev. Ц 1995. Ц Vol. 6:153Ц166.

63. Ladenvall P, Johansson L, Jansson JH, Jern S, Nilsson TK, Tjdrnlund A, Jern C, Boman K.Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction // Thromb Haemost. Ц 2002. Ц Vol. 87(1). Ц P. 105-9.

64. Tjarnlund-Wolf A, Hultman K, Curtis MA, Faull RL, Medcalf RL, Jern C. Allelic imbalance of tissue-type plasminogen activator (t-PA) gene expression in human brain tissue // Thromb Haemost. Ц 2011. Ц Vol. 105 (6). Ц P. 945-53.

65. Oguzulgen IK, Ekim N, Erkekol FO, Altinok B, Akar N.Is tissue-plasminogen activator gene polymorphism a risk factor for venous thromboembolism in every population // Thromb Thrombolysis. Ц 2005. Ц Vol. 19(1). Ц P. 61-3.

66. Hooper WC, El-Jamil M, Dilley A, Philipp C, Ellingsen D, Phillips D, Evatt BL. The relationship between the tissue plasminogen activator Alu I/D polymorphism and venous thromboembolism during pregnancy // Thromb Res. Ц 2001. Ц Vol. 102(1). Ц P. 33-7.

67. Medina P, Navarro S, Estellis A, Espasa F. Polymorphisms in the endothelial protein C receptor gene and thrombophilia // Thromb Haemost. Ц 2007. Ц Vol. 98(3). Ц P. 564-9.

68. Van de Wouwer M, Collen D, Conway EM. Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation // Arteriosclerosis, Thrombosis, and Vascular Biology. Ц 2004. Ц Vol. 24:1374Ц1383.

69. Villoutreix BO, Blom AM, Dahlback B. Structural prediction and analysis of endothelial cell protein C/activated protein C receptor // Protein Eng. Ц 1999. Ц Vol. 12. Ц P. 833-840.

70. Qu D, Wang Y, Song Y, Esmon NL, Esmon CT. The Ser219→Gly dimorphism of the endothelial protein C receptor contributes to the higher soluble protein levels observed in individuals with the A3 haplotype // Thromb Haemost. Ц 2006. Ц Vol. 4. Ц P. 229-235.

71. Saposnik B, Reny JL, Gaussem P, Emmerich J, Aiach M, Gandrille S.A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis // Blood. Ц 2004. Ц Vol. 103(4). Ц P. 1311-8.

72. Chen XD, Tian L, Li M, Jin W, Zhang HK, Zheng CF.Relationship between endothelial cell protein C receptor gene 6936A/G polymorphisms and deep venous thrombosis // Chin Med J (Engl). Ц 2011. Ц Vol. 124(1). Ц P. 72-5.

73. Dennis J, Johnson CY, Adediran AS, de Andrade M, Heit JA, Morange PE, Trigoult DA, Gagnon F. The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies // Blood. Ц 2012. Ц Vol. 119(10). Ц P. 2392-400.

74. Medina P, Navarro S, Estellis A, Vayb A, Woodhams B, Mira Y, Villa P, Migaud-Fressart M, Ferrando F, Aznar J, Bertina RM, Espasa F.Research Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk // Thromb Haemost. Ц 2004. Ц Vol. 91(5). Ц P. 905-11.

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