open access

Vol 88, No 7 (2017)
Research paper
Published online: 2017-07-31
Get Citation

Contribution of inherited thrombophilia to recurrent miscarriage in the Polish population

Hubert Wolski12, Magdalena Barlik13, Krzysztof Drews13, Andrzej Klejewski45, Grażyna Kurzawińska3, Marcin Ożarowski6, Zdzisław Łowicki6, Agnieszka Seremak-Mrozikiewicz136
DOI: 10.5603/GP.a2017.0072
·
Pubmed: 28819944
·
Ginekol Pol 2017;88(7):385-392.
Affiliations
  1. Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
  2. Division of Gynecology and Obstetrics, Podhale Multidisciplinary Hospital, Nowy Targ, Poland
  3. Laboratory of Molecular Biology, Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
  4. Department of Nursing, Poznan University of Medical Sciences, Poznan, Poland Poznan, Poland
  5. Department of Obstetrics and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
  6. Department of Pharmacology and Phytochemistry, Institute of Natural Fibers and Medicinal Plants, Poznan, Poland

open access

Vol 88, No 7 (2017)
ORIGINAL PAPERS Obstetrics
Published online: 2017-07-31

Abstract

Introduction: The aim of the study was to evaluate the contribution of genetic variants determining inherited thrombophilia to recurrent miscarriage (RM) in the Polish population. The following polymorphisms were analyzed: 1691G>A, 1328T>C of coagulation factor V, 20210G>A of coagulation factor II, R353Q (11496G>A) of coagulation factor VII, 667C>T, 1298A>C, 1793G>A of MTHFR.

Material and methods: A total of 359 women with ≥ 2 subsequent recurrent miscarriages (303 < 13 weeks of gestation (w.g.) and 56 between 13–22 w.g.) and 400 healthy controls were included in the study. Frequency of the genetic polymor­phisms was determined with the PCR/RFLP method.

Results: Higher frequency of the 20210GA genotype was found in the RM < 13 w.g. (2.97 vs. 1.50% in controls, OR = 2.01, ns) and the RM 13–22 w.g. (5.36 vs. 1.50% in controls, OR = 3.72, p = 0.09) subgroups. Statistically significantly higher frequency of the 11496GA genotype was noted in controls as compared to the RM 13–22 w.g. subgroup (10.71 vs. 23.00% in controls, OR = 0.40, p = 0.02). Statistically significantly higher frequency of the 1793GA genotype was observed in the RM < 13 w.g. subgroup as compared to controls (12.21 vs. 7.75% in controls, OR = 1.66, p = 0.03). No significant correlations were found as far as the rest of the analyzed polymorphisms are concerned.

Conclusions: The obtained results suggest that the 1793G>A MTHFR, R353Q (11496G>A) factor VII gene and the 20210G>A factor II gene polymorphisms play a role in the etiology of RM in the Polish population.

Abstract

Introduction: The aim of the study was to evaluate the contribution of genetic variants determining inherited thrombophilia to recurrent miscarriage (RM) in the Polish population. The following polymorphisms were analyzed: 1691G>A, 1328T>C of coagulation factor V, 20210G>A of coagulation factor II, R353Q (11496G>A) of coagulation factor VII, 667C>T, 1298A>C, 1793G>A of MTHFR.

Material and methods: A total of 359 women with ≥ 2 subsequent recurrent miscarriages (303 < 13 weeks of gestation (w.g.) and 56 between 13–22 w.g.) and 400 healthy controls were included in the study. Frequency of the genetic polymor­phisms was determined with the PCR/RFLP method.

Results: Higher frequency of the 20210GA genotype was found in the RM < 13 w.g. (2.97 vs. 1.50% in controls, OR = 2.01, ns) and the RM 13–22 w.g. (5.36 vs. 1.50% in controls, OR = 3.72, p = 0.09) subgroups. Statistically significantly higher frequency of the 11496GA genotype was noted in controls as compared to the RM 13–22 w.g. subgroup (10.71 vs. 23.00% in controls, OR = 0.40, p = 0.02). Statistically significantly higher frequency of the 1793GA genotype was observed in the RM < 13 w.g. subgroup as compared to controls (12.21 vs. 7.75% in controls, OR = 1.66, p = 0.03). No significant correlations were found as far as the rest of the analyzed polymorphisms are concerned.

Conclusions: The obtained results suggest that the 1793G>A MTHFR, R353Q (11496G>A) factor VII gene and the 20210G>A factor II gene polymorphisms play a role in the etiology of RM in the Polish population.

Get Citation

Keywords

recurrent miscarriage, inherited thrombophilia, genetic polymorphism

About this article
Title

Contribution of inherited thrombophilia to recurrent miscarriage in the Polish population

Journal

Ginekologia Polska

Issue

Vol 88, No 7 (2017)

Article type

Research paper

Pages

385-392

Published online

2017-07-31

DOI

10.5603/GP.a2017.0072

Pubmed

28819944

Bibliographic record

Ginekol Pol 2017;88(7):385-392.

Keywords

recurrent miscarriage
inherited thrombophilia
genetic polymorphism

Authors

Hubert Wolski
Magdalena Barlik
Krzysztof Drews
Andrzej Klejewski
Grażyna Kurzawińska
Marcin Ożarowski
Zdzisław Łowicki
Agnieszka Seremak-Mrozikiewicz

References (33)
  1. Saito S. The causes and treatment of recurrent pregnancy loss. JMAJ. 2009; 52: 97–102.
  2. Rambaldi MP, Mecacci F, Guaschino S, et al. Inherited and acquired thrombophilias. Reprod Sci. 2014; 21(2): 167–182.
  3. Middeldorp S. Anticoagulation in pregnancy complications. Hematology Am Soc Hematol Educ Program. 2014; 2014(1): 393–399.
  4. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009; 2(2): 76–83.
  5. Alonso A, Soto I, Urgellés MF, et al. Acquired and inherited thrombophilia in women with unexplained fetal losses. Am J Obstet Gynecol. 2002; 187(5): 1337–1342.
  6. Bennett SA, Bagot CN, Arya R. Pregnancy loss and thrombophilia: the elusive link. Br J Haematol. 2012; 157(5): 529–542.
  7. Vaiman D. Genetic regulation of recurrent spontaneous abortion in humans. Biomed J. 2015; 38(1): 11–24.
  8. Cao Y, Zhang Z, Xu J, et al. The association of idiopathic recurrent pregnancy loss with polymorphisms in hemostasis-related genes. Gene. 2013; 530(2): 248–252.
  9. Carp H, Salomon O, Seidman D, et al. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod. 2002; 17(6): 1633–1637.
  10. Greer IA. Thrombophilia: implications for pregnancy outcome. Thromb Res. 2003; 109(2-3): 73–81.
  11. Kupferminc JM. Management of thrombophilia in women with PVC. Thromb Res. 2005; 115 Suppl 1: 46–50.
  12. Onderoglu L, Baykal C, Al RA, et al. High frequency of thrombophilic disorders in women with recurrent fetal miscarriage. Clin Exp Obstet Gynecol. 2006; 33(1): 50–54.
  13. Robertson L, Wu O, Langhorne P, et al. Thrombophilia in pregnancy: a systemic review. Br J Haematol. 2006; 132: 171–196.
  14. Johnson CM, Mureebe L, Silver D. Hypercoagulable states: a review. Vasc Endovascular Surg. 2005; 39(2): 123–133.
  15. McNamee KM, Dawood F, Farquharson RG, et al. Thrombophilia and early pregnancy loss. Best Pract Res Clin Obstet Gynaecol. 2012; 26(1): 91–102.
  16. Singer JB. Candidate gene association analysis. Methods Mol Biol. 2009; 573: 223–230.
  17. Skrzypczak J, Rajewski M, Wirstlein P, et al. [Incidence of hereditary thrombophilia in women with pregnancy loss in multi-center studies in Poland]. Ginekol Pol. 2012; 83(5): 330–336.
  18. Sergi C, Al Jishi T, Walker M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch Gynecol Obstet. 2015; 291(3): 671–679.
  19. Baumann K, Beuter-Winkler P, Hackethal A, et al. Maternal factor V Leiden and prothrombin mutations do not seem to contribute to the occurrence of two or more than two consecutive miscarriages in Caucasian patients. Am J Reprod Immunol. 2013; 70(6): 518–521.
  20. Bałajewicz-Nowak M, Pityński K, Milewicz T. [The 1691 G > A (factor V Leiden) and 1328 T > C V coagulation factor polymorphisms and recurrent miscarriages]. Ginekol Pol. 2015; 86(1): 46–52.
  21. Barlik M, Seremak-Mrozikiewicz A, Kraśnik W, et al. [The 20210G>A and 19911A>G polymorphisms of prothrombin gene and recurrent miscarriages]. Ginekol Pol. 2013; 84(10): 830–834.
  22. Gao H, Tao Fb. Prothrombin G20210A mutation is associated with recurrent pregnancy loss: a systematic review and meta-analysis update. Thromb Res. 2015; 135(2): 339–346.
  23. Mrozikiewicz PM, Cascorbi I, Ziemer S, et al. Reduced procedural risk for coronary catheter interventions in carriers of the coagulation factor VII-Gln353 gene. J Am Coll Cardiol. 2000; 36(5): 1520–1525.
  24. Seremak-Mrozikiewicz A, Drews K, Kurzawińska G, et al. Związek polimorfizmu Arg353Gln czynnika VII krzepnięcia z poronieniami nawracającymi. Ginekol Pol. 2009; 80: 8–13.
  25. Seremak-Mrozikiewicz A, Drews K, Kurzawinska G, et al. The significance of 1793G>A polymorphism in MTHFR gene in women with first trimester recurrent miscarriages. Neuro Endocrinol Lett. 2010; 31(5): 717–723.
  26. Robertson L, Wu O, Langhorne P, et al. Thrombophilia in pregnancy: a systemic review. Br J Haematol. 2006; 132: 171–196.
  27. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10(1): 111–113.
  28. Hanson NQ, Aras O, Yang F, et al. C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease. Clin Chem. 2001; 47(4): 661–666.
  29. Rady PL, Szucs S, Grady J, et al. Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A. Am J Med Genet. 2002; 107(2): 162–168.
  30. 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): 64–67.
  31. Faisel F, Romppanen EL, Hiltunen M, et al. Susceptibility to pre-eclampsia in Finnish women is associated with R485K polymorphism in the factor V gene, not with Leiden mutation. Eur J Hum Genet. 2004; 12(3): 187–191.
  32. Poort SR, Rosendaal FR, Reitsma PH, et al. A common genetic variation in the 3-prime-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996; 88: 3698–3703.
  33. Green F, Kelleher C, Wilkes H, et al. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb. 1991; 11(3): 540–546.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk
tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl