blogger delicious digg diigo facebook googleplus linkedin netlog reddit twitter
Skip Navigation LinksJRI > Archive > January-March 2009, Volume 9, Issue 4 > The Relationship between Polymorphisms of Blood Coagulation Factor V Gene and Recurrent Pregnancy Losses



Volume 9, Issue 4, Number 37 / January-March
(pages 305-316)


The Relationship between Polymorphisms of Blood Coagulation Factor V Gene and Recurrent Pregnancy Losses




Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran

Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran

Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran

Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran

Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

 Corresponding Author
Monoclonal Antibody Research Center, Avicenna Research Institute (ACECR), Tehran, Iran

Received: 10/26/2008 Accepted: 1/8/2009

Related Articles
in Google Scholar in PubMed

 

Other Format
pdfPDF Full Text (En) pdfPDF Full Text (Fa) pdfePUB Full Text (En) pdfPDF Abstract (En) pdfPDF Abstract (Fa) pdf BibTeX pdfRefMan pdfEndNote xmlPMC XML online readerPMC Reader

 


Abstract
Introduction: Polymorphisms of coagulation factor V gene are the most important suspected causes of thrombophilia in women with recurrent pregnancy losses (RPL). In this study the association between three polymorphisms of factor V (FV Leiden, FV A4070G & FV A5279G) and RPL are sought in Iranian women.Materials & Methods: In this case-control study, 100 female patients with at least two recurrent abortions were selected as the cases, and 100 healthy women with a history of two successful deliveries as the controls. Peripheral blood samples were collected and DNA was extracted. PCR-RFLP method was used for genotyping the samples.Results: Regarding the prevalence of FV Leiden mutation in the cases and the controls, 13% and 4% respectively, the chances for recurrent pregnancy losses were more than 3.5 times higher in individuals with this polymorphism (OR: 3.586, 95% CI: 1.127–11.412). The frequencies of FV A4070G and FV A5279G were 14% and 37% in the case and 4% and 7% in the control groups, respectively and the chances for RPL were higher in cases with these two polymorphisms. The proportion of cases with two or three mutations in the gene in comparison with the controls, showed a significant correlation between FV Leiden and FV A4070G polymorphisms. Statistical analysis of the simultaneous effects of the three polymorphisms for RPL showed that evaluation of FV A4070G and FV A5279G could help assess the chances of the three mutations for RPL.Conclusion: The three polymorphisms in coagulation V gene are accompanied with increased risks for RPL. Evaluation for the three polymorphisms is suggested in the work up of women with RPL.

Keywords: Blood coagulation factor V, FV A4070G, FV A5279G, FV Leiden, Polymorphism, Recurrent Pregnancy Loss, Thrombophilia


To cite this article:



Figures, Charts, Tables

References
  1. Tulppala M, Ylikorkala O. Recurrent spontaneous abortion: where do we stand now? Ann Med. 1991; 23(6): 603-4.   [PubMed]
  2. Tulppala M, Palosuo T, Ramsay T, Miettinen A, Salonen R, Ylikorkala O. A prospective study of 63 couples with a history of recurrent spontaneous abor-tion: contributing factors and outcome of subsequent pregnancies. Hum Reprod. 1993; 8(5): 764-70.   [PubMed]
  3. Glueck CJ, Gogenini S, Munjal J, Tracy T, Pranikoff J, Wang P. Factor V Leiden mutation: a treatable etiology for sporadic and recurrent pregnancy loss. Fertil Steril. 2008; 89(2): 410-6.   [PubMed]
  4. Baek KH, Lee EJ, Kim YS. Recurrent pregnancy loss: the key potential mechanisms. Trends Mol Med. 2007; 13(7): 310-7.   [PubMed]
  5. Zammiti W, Mtiraoui N, Mercier E, Abboud N, Saidi S, Mahjoub T, et al. Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2 haplotype) with recurrent idiopathic pregnancy loss in Tunisia. A case-control study. Thromb Haemost. 2006; 95(4): 612-7.   [PubMed]
  6. Younis JS, Brenner B, Ohel G, Tal J, Lanir N, Ben-Ami M. Activated protein C resistance and factor V Leiden mutation can be associated with first-as well as second-trimester recurrent pregnancy loss. Am J Reprod Immunol. 2000; 43(1): 31-5.   [PubMed]
  7. Wramsby ML, Sten-Linder M, Bremme K. Primary habitual abortions are associated with high frequency of factor V Leiden mutation. Fertil Steril. 2000; 74(5): 987-91.   [PubMed]
  8. Wolf CE, Haubelt H, Pauer HU, Hinney B, Krome-Cesar C, Legler TJ, et al. Recurrent pregnancy loss and its relation to FV Leiden, FII G20210A and poly-morphisms of plasminogen activator and plasminogen activator inhibitor. Pathophysiol Haemost Thromb. 2003; 33(3): 134-7.   [PubMed]
  9. Pauer HU, Voigt-Tschirschwitz T, Hinney B, Burfeind P, Wolf C, Emons G, et al. Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand. 2003; 82(10): 942-7.   [PubMed]
  10. Hopmeier P, Puehringer H, van Trotsenburg M, Atamaniuk J, Oberkanins C, Dossenbach-Glaninger A. Association of endothelial protein C receptor haplo-types, factor V Leiden and recurrent first trimester pregnancy loss. Clin Biochem. 2008; 41(12): 1022-4.   [PubMed]
  11. Goodman CS, Coulam CB, Jeyendran RS, Acosta VA, Roussev R. Which thrombophilic gene mutations are risk factors for recurrent pregnancy loss? Am J Reprod Immunol. 2006; 56(4): 230-6.   [PubMed]
  12. Glueck CJ, Wang P, Bornovali S, Goldenberg N, Sieve L. Polycystic ovary syndrome, the G1691A factor V Leiden mutation, and plasminogen activator inhibitor activity: associations with recurrent preg-nancy loss. Metabolism. 2003; 52(12): 1627-32.   [PubMed]
  13. Glueck CJ, Pranikoff J, Aregawi D, Haque M, Zhu B, Tracy T, et al. The factor V Leiden mutation, high factor VIII, and high plasminogen activator inhibitor activity: etiologies for sporadic miscarriage. Metabol-ism. 2005; 54(10): 1345-9.   [PubMed]
  14. Foka ZJ, Lambropoulos AF, Saravelos H, Karas GB, Karavida A, Agorastos T, et al. Factor V leiden and prothrombin G20210A mutations, but not methylen-etetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod. 2000; 15(2): 458-62.   [PubMed]
  15. Foka ZJ, Lambropoulos AF, Makris PE, Constan-tinidis TC, Kotsis A. High frequency of factor V Leiden and prothrombin G20210A mutations in Greek hemophiliacs. J Thromb Haemost. 2003; 1(5): 1116-7.   [PubMed]
  16. Behjati R, Modarressi MH, Jeddi-Tehrani M, Dokoohaki P, Ghasemi J, Zarnani AH, et al. Thrombo-philic mutations in Iranian patients with infertility and recurrent spontaneous abortion. Ann Hematol. 2006; 85(4): 268-71.   [PubMed]
  17. Yamada H, Sata F, Saijo Y, Kishi R, Minakami H. Genetic factors in fetal growth restriction and miscar-riage. Semin Thromb Hemost. 2005; 31(3): 334-45. Review.   [PubMed]
  18. Raziel A, Kornberg Y, Friedler S, Schachter M, Sela BA, Ron-El R. Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss. Am J Reprod Immunol. 2001; 45(2): 65-71.   [PubMed]
  19. Rai R, Shlebak A, Cohen H, Backos M, Holmes Z, Marriott K, et al. Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage. Hum Reprod. 2001; 16(5):961-5.   [PubMed]
  20. Pihusch R, Buchholz T, Lohse P, Rübsamen H, Rogenhofer N, Hasbargen U, et al. Thrombophilic gene mutations and recurrent spontaneous abortion: pro-thrombin mutation increases the risk in the first trimester. Am J Reprod Immunol. 2001; 46(2): 124-31.   [PubMed]
  21. Ozcan T, Rinder HM, Murphy J. Genetic throm-bophilia mutations are not increased in patients with recurrent losses. Obstet Gynecol. 2001; 97(4 Suppl 1): S31.
  22. Nowak-G?ttl U, Sonntag B, Junker R, Cirkel U, von Eckardstein A. Evaluation of lipoprotein(a) and genetic prothrombotic risk factors in patients with recurrent foetal loss. Thromb Haemost. 2000; 83(2): 350-1.   [PubMed]
  23. Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol. 2006; 55(5): 360-8.   [PubMed]
  24. Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombo-philia in recurrent pregnancy loss. Hum Reprod. 2002; 17(6): 1633-7.   [PubMed]
  25. Alonso A, Soto I, Urgellés MF, Corte JR, Rodr?guez MJ, Pinto CR. Acquired and inherited thrombophilia in women with unexplained fetal losses. Am J Obstet Gynecol. 2002; 187(5): 1337-42.   [PubMed]
  26. Strey RF, Siegemund A, Siegemund T, Schubert C, Schuster G, Wulff K, et al. Influence of factor V HR2 on thrombin generation and clinical manifestation in rare bleeding disorders. Pathophysiol Haemost Thromb. 2005; 34(6): 279-83.   [PubMed]
  27. Soria JM, Blangero J, Souto JC, Mart?nez-S?nchez E, Mart?nez-March?n E, Coll I, et al. Identification of a large deletion and three novel mutations in exon 13 of the factor V gene in a Spanish family with normal factor V coagulant and anticoagulant properties. Hum Genet. 2002; 111(1): 59-65.   [PubMed]
  28. Otrock ZK, Taher AT, Shamseddeen WA, Zaatari G, Bazarbachi A, Mahfouz RA. Factor V HR2 haplotype: a risk factor for venous thromboembolism in individ-uals with absence of Factor V Leiden. Ann Hematol. 2008; 87(12): 1013-6.   [PubMed]
  29. Castoldi E, Simioni P, Kalafatis M, Lunghi B, Tormene D, Girelli D, et al. Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family. Blood. 2000; 96(4): 1443-8.   [PubMed]
  30. Castoldi E, Lunghi B, Mingozzi F, Simioni P, Girolami A, Bernardi F. A highly polymorphic microsatellite in the factor V gene is an informative tool for the study of factor V-related disorders. Br J Haematol. 2001; 114(4): 868-70.   [PubMed]
  31. Castoldi E, Brugge JM, Nicolaes GA, Girelli D, Tans G, Rosing J. Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations. Blood. 2004; 103(11): 4173-9.   [PubMed]
  32. Zammiti W, Mtiraoui N, Mercier E, Abboud N, Saidi S, Mahjoub T, et al. Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2 haplotype) with recurrent idiopathic pregnancy loss in Tunisia. A case-control study. Thromb Haemost. 2006; 95(4): 612-7.   [PubMed]
  33. van Wijk R, Nieuwenhuis K, van den Berg M, Huizinga EG, van der Meijden BB, Kraaijenhagen RJ, et al. Five novel mutations in the gene for human blood coagulation factor V associated with type I factor V deficiency. Blood. 2001; 98(2): 358-67.   [PubMed]
  34. Castoldi E, Lunghi B, Mingozzi F, Muleo G, Redaelli R, Mariani G, et al. A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor V deficiency in the Italian population. Haematologica. 2001; 86(6): 629-33.   [PubMed]
  35. Yamakage N, Ikejiri M, Okumura K, Takagi A, Murate T, Matushita T, et al. A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene. Haemophilia. 2006; 12(2): 172-8.   [PubMed]
  36. Jivraj S, Rai R, Underwood J, Regan L. Genetic thrombophilic mutations among couples with recurrent miscarriage. Hum Reprod. 2006; 21(5): 1161-5.   [PubMed]
  37. Z?ller B, Svensson PJ, He X, Dahlb?ck B. Identifica-tion of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest. 1994; 94(6): 2521-4.   [PubMed]
  38. Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet. 1993; 342 (8886-8887): 1503-6.   [PubMed]
  39. Zeinali S, Duca F, Zarbakhsh B, Tagliabue L, Mannucci PM. Thrombophilic mutations in Iran. Thromb Haemost. 2000; 83(2): 351-2.   [PubMed]
  40. Zahed LF, Rayes RF, Mahfouz RA, Taher AT, Maarouf HH, Nassar AH. Prevalence of factor V Leiden, prothrombin and methylene tetrahydrofolate reductase mutations in women with adverse pregnancy outcomes in Lebanon. Am J Obstet Gynecol. 2006; 195(4): 1114-8.   [PubMed]
  41. Murphy RP, Donoghue C, Nallen RJ, D Mello M, Regan C, Whitehead AS, et al. Prospective evaluation of the risk conferred by factor V Leiden and thermo-labile methylenetetrahydrofolate reductase polymorph-isms in pregnancy. Arterioscler Thromb Vasc Biol. 2000; 20(1): 266-70.   [PubMed]
  42. Azem F, Many A, Ben Ami I, Yovel I, Amit A, Lessing JB, et al. Increased rates of thrombophilia in women with repeated IVF failures. Hum Reprod. 2004; 19(2): 368-70.   [PubMed]
  43. Castaman G, Faioni EM, Tosetto A, Bernardi F. The factor V HR2 haplotype and the risk of venous throm-bosis: a meta-analysis. Haematologica. 2003; 88(10): 1182-9.   [PubMed]
  44. Yamada H, Kato EH, Kobashi G, Ebina Y, Shimada S, Morikawa M, et al. Recurrent pregnancy loss: etiology of thrombophilia. Semin Thromb Hemost. 2001; 27(2): 121-9. Review.   [PubMed]



Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and copyrighted by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2016 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.