Journal of Thrombosis and Thrombolysis

, Volume 30, Issue 1, pp 97–104

The significance of genetic polymorphisms of factor V leiden and prothrombin in the preeclamptic polish women

  • Agnieszka Seremak-Mrozikiewicz
  • Krzysztof Drews
  • Ewa Wender-Ożegowska
  • Przemyslaw M. Mrozikiewicz
Article

Abstract

Many studies established that gestational hypertension (GH) and preeclampsia (PE) are multifactorial diseases and disturbances in coagulation cascade have etiological significance. Inherited thrombophilias, like polymorphism of factor V (FV) Leiden and prothrombin (PTM) are considered to be involved in the PE development. The aim of this study was to determine the association between FV Leiden and G20210A of PTM gene polymorphism and GH/PE appearance. The study comprised 235 women: GH (n = 126, mean age 27.5 ± 6.0 years), mild PE (n = 41, mean age 28.3 ± 5.7 years), and severe PE (n = 68, mean age 28.5 ± 5.7 years). The control group consisted of 400 healthy pregnant women (mean age 27.5 ± 4.7 years). All women included in the study were white Caucasian of Polish origin, and were singleton pregnancies. The G1691A polymorphism of FV and G20210A polymorphism of PTM were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assays. For PTMG20210A polymorphism overrepresentation of heterozygous GA genotype (7.4 vs. 1.2%, P = 0.02) and of A allele (3.7 vs. 0.6%, P = 0.02) in the group of severe PE have been found. For FVG1691A polymorphism the overrepresentation of genotypes containing at least one mutated allele A (GA and AA) in the group of women with mild (9.7 vs. 3.5%, ns) and severe PE (8.8 vs. 3.5%, ns) was observed. Our results suggest the significant influence of G20210A prothrombin polymorphism and possible influence of G1691A factor V polymorphism in the development of severe preeclampsia.

Keywords

Gestational hypertension Preeclampsia Hereditary thrombophilia Genetic polymorphism 

References

  1. 1.
    Pabinger I (2008) Thrombophilia and its impact on pregnancy. Hamostaseologie 28(3):130–134PubMedGoogle Scholar
  2. 2.
    Blickstein I (2006) Thrombophilia and women’s health: an overview. Obstet Gynecol Clin North Am 33(3):347–356CrossRefPubMedGoogle Scholar
  3. 3.
    Adelberg AM, Kuller JA (2002) Thrombophilias and recurrent miscarriage. Obstet Gynecol Surv 57(10):703–709CrossRefPubMedGoogle Scholar
  4. 4.
    Agorastos T, Karavida A, Lambropoulos A, Constantinidis T, Tzitzimikas S (2002) Factor V Leiden and prothrombin G20210A mutations in pregnancies with adverse outcome. J Matern Fetal Neonatal Med 12(4):267–273PubMedGoogle Scholar
  5. 5.
    Mahjoub T, Mtiraoui N, Tamim H, Hizem H, Finan RR, Nsiri B, Almawi WY (2005) Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages. Am J Hematol 80(1):12–19CrossRefPubMedGoogle Scholar
  6. 6.
    Facchinetti F, Marozio L, Grandone E, Pizzi C, Volpe A, Benedetto C (2003) Thrombophilic mutations are a main risk factor for placental abruption. Haematologica 88(7):785–788PubMedGoogle Scholar
  7. 7.
    Tempfer CB, Jirecek S, Riener EK, Zeisler H, Denschlag D, Hefler L, Husslein PW (2004) Polymorphisms of thrombophilic and vasoactive genes and severe preeclampsia: a pilot study. J Soc Gynecol Invest 11(4):227–231CrossRefGoogle Scholar
  8. 8.
    Kupferminc MJ (2005) Thrombophilia and pregnancy. Curr Pharm Des 11(6):735–848CrossRefPubMedGoogle Scholar
  9. 9.
    Kupferminc MJ (2005) Thrombophilia and preeclampsia: the evidence so far. Clin Obstet Gynecol 48(2):406–415CrossRefPubMedGoogle Scholar
  10. 10.
    Cohen SM (2004) Factor V Leiden mutation in pregnancy. J Obstet Gynecol Neonatal Nurs 33(3):348–353CrossRefPubMedGoogle Scholar
  11. 11.
    Dahlback B (1994) Inherited resistance to activated protein C, a major cause of venous thrombosis, is due to a mutation in the factor V gene. Haemostasis 24(2):139–151PubMedGoogle Scholar
  12. 12.
    Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:14–15CrossRefGoogle Scholar
  13. 13.
    Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) 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 88(10):3698–3703PubMedGoogle Scholar
  14. 14.
    Dahlback B (2008) Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 112(1):19–27CrossRefPubMedGoogle Scholar
  15. 15.
    Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy (2000) Am J Obstet Gynecol 183(1): 1–22Google Scholar
  16. 16.
    Roberts JM, Lain KY (2002) Recent insights into the pathogenesis of preeclampsia. Placenta 23(5):359–372CrossRefPubMedGoogle Scholar
  17. 17.
    Middeldrop S (2007) Thrombophilia and pregnancy complications: cause or association? J Thromb Haemost 5(1):276–282CrossRefGoogle Scholar
  18. 18.
    Mello G, Parretti E, Marozio L, Pizzi C, Lojacono A, Frusca T, Facchinetti F, Benedetto C (2005) Thrombophilia is significantly associated with severe preeclampsia. Results of a large-scale, case controlled study. Hypertension 46(6):1270–1274CrossRefPubMedGoogle Scholar
  19. 19.
    Chan MY, Andreotti F, Becker RC (2008) Hypercoagulable states in cardiovascular disease. Circulation 118(22):2286–2297CrossRefPubMedGoogle Scholar
  20. 20.
    Myatt L, Webster RP (2009) Vascular biology of preeclampsia. J Thromb Haemost 7(3):375–384CrossRefPubMedGoogle Scholar
  21. 21.
    Wang A, Rana S, Karumanchi SA (2009) Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda) 24:147–158Google Scholar
  22. 22.
    Dizon-Townson DS, Nelson LM, Easton K, Ward K (1996) The factor V Leiden mutation may predispose women to severe preeclampsia. Am J Obstet Gynecol 175(4):902–905CrossRefPubMedGoogle Scholar
  23. 23.
    Lin J, August P (2005) Genetic thrombophilias and preeclampsia: a meta-analysis. Obstet Gynecol 105(1):182–192PubMedGoogle Scholar
  24. 24.
    Dudding T, Heron J, Thakkinstian A, Nurk E, Golding J, Pembrey M, Ring SM, Attia J, Scott RJ (2008) Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis. J Thromb Haemost 6(11):1869–1875CrossRefPubMedGoogle Scholar
  25. 25.
    D’Elia AV, Driul L, Giacommello R, Colaone R, Fabbro D, Di Leonardo C, Florio P, Petraglia F, Marchesoni D, Damante G (2002) Frequency of factor V, prothrombin and methylenetetra and hydrofolate raductase gene variants in preeclampsia. Gynecol Obstet Invest 53(2):84–87CrossRefPubMedGoogle Scholar
  26. 26.
    Dusse LM, Carvalho MG, Braganca WF, Paiva SG, Godoi LC, Guimaraes DA, Fernandes AP (2007) Inherited thropmbophilias and pre-eclampsia in Brazilian women. Eur J Obstet Gynecol Reprod Biol 134(1):20–23CrossRefPubMedGoogle Scholar
  27. 27.
    De Maat MP, Jansen MW, Hille ET, Vos HL, Bloemenkamp KW, Buitendijk S, Helmerhorst FM, Wladimiroff JW, Bertina RM, De Groot CJ (2004) Preeclampsia and its interaction with common variants in thrombophilia genes. J Thromb Haemost 2(9):1588–1593CrossRefPubMedGoogle Scholar
  28. 28.
    Jarvenpaa J, Pakkila M, Savolainen ER, Perheentupa A, Jarvela I, Ryynanen M (2006) Evaluation of factor V Leiden, prothrombin and methylene tetrahydrofolate reductase gene mutations in patients with severe pregnancy complications in northern Finland. Gynecol Obstet Invest 62(1):28–32CrossRefPubMedGoogle Scholar
  29. 29.
    Dizon-Townson D, Miller C, Sibai B, Spong CY, Thom E, Wendel G Jr, Wenstrom K, Samuels P, Cotroneo MA, Moawad A, Sorokin Y, Meis P, Miodovnik M, O’Sullivan MJ, Conway D, Wapner RJ, Gabbe SG (2005) National institute of child health and human development maternal-fetal medicine units network. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol 106(3):517–524PubMedGoogle Scholar
  30. 30.
    ACOG Committee on Obstetric Practice (2002) ACOG practice bulletin. Diagnosis, management of preeclampsia, eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 77(1):67–75CrossRefGoogle Scholar
  31. 31.
    Sibai BM (2005) Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 105(2):402–410PubMedGoogle Scholar
  32. 32.
    Heyborne KD (2000) Preeclampsia prevention: lessons from the low-dose aspirin therapy trials. Am J Obstet Gynecol 183(3):523–528CrossRefPubMedGoogle Scholar
  33. 33.
    Shastry BS (2002) SNP alleles in human disease and evolution. J Hum Genet 47(11):561–566CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Agnieszka Seremak-Mrozikiewicz
    • 1
  • Krzysztof Drews
    • 1
  • Ewa Wender-Ożegowska
    • 2
  • Przemyslaw M. Mrozikiewicz
    • 3
    • 4
  1. 1.Division of Perinatology and Women’s Diseases, Department of Perinatology and GynecologyPoznan University of Medical SciencesPoznanPoland
  2. 2.Department of Obstetrics and Women DiseasesPoznan University of Medical SciencesPoznanPoland
  3. 3.Department of Clinical Pharmacy and BiopharmacyPoznan University of Medical SciencesPoznanPoland
  4. 4.Department of Pharmacology and BiotechnologyInstitute of Natural Fibers and Medicinal PlantsPoznanPoland

Personalised recommendations