The association of factor V G1961A (factor V Leiden), prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women
Aim To investigate association of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Methods A total of 60 women with two or more consecutive miscarriages before 20 weeks of gestation with the same partners and without history of known causes or recurrent pregnancy loss were included. A control group included 80 healthy women who had one or more successful pregnancies without history of any complication which could be associated with miscarriages. Genotyping of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms were performed by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). Results Both factor V Leiden and MTHFR C677T polymorphisms were significantly associated with recurrent pregnancy loss (RPL) in Bosnian women while prothrombin G20210A and PAI-1 4G/5G polymorphisms did not show strongly significant association. Conclusion The presence of thrombophilic polymorphisms may predispose women to recurrent pregnancy loss. Future investigation should be addressed in order to find when carriers of those mutations, polymorphisms should be treated with anticoagulant therapy.
Finan R, Tamim H, Ameen G, Sharida H, Rashid M, Almawi W. Prevalence of factor V G1691A (Factor V Leiden) and prothrombin gene mutations in a recurrent miscarriage population. Am J Hematol 2002:300–5.
2
Bertina R, Koelman B, Koster T, Rosendaal F, Dirven R, De Ronde H, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1996:64–7.
3
Froost P, Blom H, Milos R, Goyette P, Sheppard C, Matthews R, et al. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolatereductase. Nat Genet 1995:111–3.
4
Margaglione M, Grandone E, Cappucci G, Colaizzo D, Giuliani N, Vecchione G, et al. An alternative method for PAI-1 promoter polymorphism. Thromb Haemost 1997;(4):605–6.
5
Hugh M, M. The odds ratio: Calculation, usage and interpretation. Biochem Med 2009:120–6.
6
El Hachem H, Crepaux V, Panloup M, Descamps P, Legendre P, G, et al. Precurrent pregnancy loss. Int J Womens Health 2017:331–45.
7
Nahas R, Saliba W, Elias A, Elias M. The prevalence of thrombophilia in women with recurrent fetal loss and outcome of anticoagulation therapy for the prevention of miscarriages. Clin Appl Thromb Hemost 2018:122–8.
8
D’uva M, Micco D, Strina P, Placido I, G. Recurrent pregnancy loss and thrombophilia. Journal of Clinical Medical Research 2010:18–22.
9
Mahmutbegovic E, Marjanovic D, Medjedovic E, Mehmetbegovic N, Dogan S, Valjevac A, et al. Prevalence of F5 1691 G>A, F2 20210 G>A and MTHFR 677 C>T polymorphisms in Bosnian women with pregnancy loss. Bos J Basic Med Sci 2017:309–14.
10
Poort S, Rosendaal F, Reitsma P, Bertina R. 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 1996:3698–703.
11
Alifirevic Z, Mousa H. Thrombophilia and adverse pregnancy outcome. Croat Med J 2001:135–45.
12
Habibovic Z, Zeybek B, Sanhal C, Eroglu Z, Karaca E, Ulukus M. Effects of inherited thrombophilia in women with recurrent pregnancy loss. Clin Exp Obstet Gynecol 2011:347–50.
13
Rai V. Methylenetetrahydrofolate reductase C677T polymorphism and recurrent pregnancy loss risk in Asian population: a meta-analysis. Indian J Clin Biochem 2016:402–13.
14
Torabi R, Zarei S, Zeraati H, Zarnani A, Akhondi M, Hadavi R, et al. Combination of thrombophilic gene polymorphisms as a casuse of increased the risk of recurrent pregnancy loss. J Reprod Infertil 2012:89–94.
15
Hefler L, Jireck S, Heim K, Grimm C, Antensteiner G, Zeiliner R, et al. Genetic polymorphisms associated with thrombophilia and vascular disease in women with unexplained late intrauterine foetal death: a multicentre study. Journal of the Society Gynecologic Investigation 2004:42–4.
16
Lykke J, Bare L, Olsen J, Lagier R, Arellano A, Tong C, et al. Langhoff-Roos J. Thrombophilias and adverse pregnancy outcomes: results from Danish National Birth Cohort. Thromb Haemost 2012:1320–5.
17
Li X, Liu Y, Zhang R, Tan J, Chen L, Liu Y. Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss. Med Sci Monit 2015:1051–6.
18
Su M, Lin S, Chen Y, Kuo P. Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Thromb Haemost 2013:8–15.
19
Karmali M, Hantoushzadeh S, Borna S, Neamatzadeh H, Mazaheri M, Noori-Shadkam M, et al. Association between thrombophilic genes polymorphisms and recurrent pregnancy loss susceptibility in the Iranian population: a systematic review and meta-analysis. Iran Biomed J 2018:78–89.
20
Bozikova A, Gabrikova D, Pitonak J, Bernasovska J, Macekova S, Beluhova-Lohajova R. Ethnic differences in the association of thrombophilic polymorphisms with obstetric complications in Slovak and Roma (Gypsy) populations. Genet Test Mol Biomarkers 2015:98–102.
21
Parand A, Zolghadri J, Nezam M, Afrasaibi A, Haghpanah S, Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red Crescent Med J 2013:13708.
22
Erol R, Schorge J. Obstetrics and Gynecology at a glance. 4 th ed 2013.
23
Coulam C, Wallis D, Weinstein J, Dasgupta D, Jejendram R. Comparison of thrombophilic gene mutations among patients experiencing recurrent miscarriage and deep vein thrombosis. Am J Reprod Immunol 2008:426–31.
24
Dawood F, Mountford R, Ferquharson R, Quenby S. Genetic polymorphisms on the factor V gene in women with recurrent miscarriage an acquired APCR. Hum Reprod 2007:2546–53.
25
Mierla D, Szmal C, Neagos D, Cretu R, Stoian V, Jardan D. Association of prothrombin (A20210G) and factor V Leiden (A506G) with recurrent pregnancy loss. J Clin Med 2012:222–6.
26
Krishnaswamy S. The transition of prothrombin to thrombin. J Thromb Haemost 2013:265–76.
27
Kujovich J. Thrombophilia and pregnancy complications. Am J Obstet Gynecol 2004:412–24.
28
Kutteh W, Triplett D. Thrombophilias and recurrent pregnancy loss. Semin Reprod Med 2006:54–6.
29
Rey E, Kahn S, David M, Shrier I. Thrombophilic disorders and foetal loss: a meta-analysis. Lancet 2003:901–8.
30
Vossen C, Preston F, Conard J, Fontcuberta J, Makris M, Van Der Meer F, et al. Rosendaal FR. Hereditary thrombophilia and fetal loss: a prospective follow-up study. J Thromb Haemost 2004:592–6.
31
Boas W, Goncalves R, Costa O, Goncalves M. Metabolism and gene polymorphisms of the folate pathway in Brazilian women with history of recurrent abortion. Rev Bras Ginecol Obstet 2015:71–6.
32
Wu X, Zhao L, He D, Tang W, Luo Y. Association between the MTHFR C677T polymorphism and recurrent pregnancy loss: a meta-analysis. Genet Test Mol Biomarkers 2012:806–11.
33
Mtiraoui N, Zammiti W, Ghanzouani L, Braham N, Saidi S, Finan R, et al. Methylenetetrahydrofolatereductase C677T and A1298C polymorphisms and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction 2006:395–401.
34
Kurzawinska G, Barlik M, Drews K, Rozicka A, Seramek-Mrozickicwicz A, Ozarowski M, et al. Coexistence of ACE (I/D) and PAI-1 (4G/5G) gene variants in recurrent miscarriage in Polish population. Ginekol Pol 2016:271–6.
35
Glueck C, Kupfermic M, Fontaine R, Wang P, Weksler B, Eldor A. Genetic hypofibrinolysis in complicated pregnancies. Obstet Gynecol 2001:44–8.
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