Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

Abstract

BACKGROUND: Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.

OBJECTIVE: The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.

METHODS: A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.

RESULTS: Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.

CONCLUSION: These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.

Key words： factor XIII; Iranian population; recurrent pregnancy loss; Val34Leu polymorphism

Acknowledgments

This work was financially supported by grant: (U-91011) from Vice-Chancellor for Research Affairs of Ahvaz Jundishapur University of Medical Sciences. We greatly appreciate the assistance provided by Dr. Zohre Sharifi of the coagulation center of Iranian blood transfusion organization. We also thank all the participants for their cooperation in the study.

Compliance with ethics guidelines

There is no conflict of interest.

References

1 Aarabi M, Memariani T, Arefi S, Aarabi M, Hantoosh Zadeh S, Akhondi M A, Modarressi M H (2011). Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme and coagulation factor XIII genes in patients with recurrent spontaneous abortion. J Matern Fetal Neonatal Med, 24(3): 545–548

PMID

2 Ariëns R A, Philippou H, Nagaswami C, Weisel J W, Lane D A, Grant P J (2000). The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. Blood, 96(3): 988–995

PMID

3 Bagheri M, Rad I A, Omrani M D, Nanbaksh F (2011). The Val34Leu genetic variation in the A subunit of coagulation factor XIII in recurrent spontaneous abortion. Syst Biol Reprod Med, 57(5): 261–264

PMID

4 Bagoly Z, Koncz Z, Hársfalvi J, Muszbek L (2012). Factor XIII, clot structure, thrombosis. Thromb Res, 129(3): 382–387

PMID

5 Balogh I, Szôke G, Kárpáti L, Wartiovaara U, Katona E, Komáromi I, Haramura G, Pfliegler G, Mikkola H, Muszbek L (2000). Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia. Blood, 96(7): 2479–2486

PMID

6 Barbosa H C, Carvalho E C, Barini R, Siqueira L H, Costa D S, Annichino-Bizzacchi J M (2004). Tyr204Phe and Val34Leu polymorphisms in two Brazilian ethnic groups and in patients with recurrent miscarriages. Fertil Steril, 82(5): 1455–1457

PMID

7 Brenner B (2002). Thrombophilia and pregnancy loss. Thromb Res, 108(4): 197–202

PMID

8 Calderwood C J, Thanoon O I (2009). Thromboembolism and thrombophilia in pregnancy. Obstetrics, Gynaecol Reprod Med, 19(12): 339–343

9 Catto A J, Kohler H P, Coore J, Mansfield M W, Stickland M H, Grant P J (1999). Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood, 93(3): 906–908

PMID

10 Coulam C B, Jeyendran R S, Fishel L A, Roussev R (2006). Multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage. Am J Reprod Immunol, 55(5): 360–368

PMID

11 de Jong P G, Goddijn M, Middeldorp S (2011). Testing for inherited thrombophilia in recurrent miscarriage. Semin Reprod Med, 29(6): 540–547

PMID

12 de Lange M, Andrew T, Snieder H, Ge D, Futers T S, Standeven K, Spector T D, Grant P J, Ariëns R A (2006). Joint linkage and association of six single-nucleotide polymorphisms in the factor XIII-A subunit gene point to V34L as the main functional locus. Arterioscler Thromb Vasc Biol, 26(8): 1914–1919

PMID

13 Diz-Kucukkaya R, Hancer V S, Inanc M, Nalcaci M, Pekcelen Y (2004). Factor XIII Val34Leu polymorphism does not contribute to the prevention of thrombotic complications in patients with antiphospholipid syndrome. Lupus, 13(1): 32–35

PMID

14 Dossenbach-Glaninger A, van Trotsenburg M, Dossenbach M, Oberkanins C, Moritz A, Krugluger W, Huber J, Hopmeier P (2003). Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin Chem, 49(7): 1081–1086

PMID

15 Elbaz A, Poirier O, Canaple S, Chédru F, Cambien F, Amarenco P (2000). The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood, 95(2): 586–591

PMID

16 Finan R R, Tamim H, Ameen G, Sharida H E, Rashid M, Almawi W Y (2002). Prevalence of factor V G1691A (factor V-Leiden) and prothrombin G20210A gene mutations in a recurrent miscarriage population. Am J Hematol, 71(4): 300–305

PMID

17 Francis C W (2002). Factor XIII polymorphisms and venous thromboembolism. Arch Pathol Lab Med, 126(11): 1391–1393

PMID

18 Franco R F, Reitsma P H, Lourenço D, Maffei F H, Morelli V, Tavella M H, Araújo A G, Piccinato C E, Zago M A (1999). Factor XIII Val34Leu is a genetic factor involved in the etiology of venous thrombosis. Thromb Haemost, 81(5): 676–679

PMID

19 Goodman C S, Coulam C B, Jeyendran R S, Acosta V A, Roussev R (2006). Which thrombophilic gene mutations are risk factors for recurrent pregnancy loss? Am J Reprod Immunol, 56(4): 230–236

PMID

20 Hancer V S, Diz-Kucukkaya R, Bilge A K, Ozben B, Oncul A, Ergen G, Nalcaci M (2006). The association between factor XIII Val34Leu polymorphism and early myocardial infarction. Circ J, 70(3): 239–242

PMID

21 Hayano Y, Imai N, Karasawa T (1982) .Studies on the physiological changes of blood coagulation factor XIII during pregnancy and their significance (author's transl). Nihon Sanka Fujinka Gakkai Zasshi, 34(4): 469–477

22 Jeddi-Tehrani M, Torabi R, Mohammadzadeh A, Arefi S, Keramatipour M, Zeraati H, Zarnani A H, Akhondi M M, Mahmoudian J, Mahmoudi A R, Zarei S (2010). Investigating association of three polymorphisms of coagulation factor XIII and recurrent pregnancy loss. Am J Reprod Immunol, 64(3): 212–217

PMID

23 Kangsadalampai S, Board P G (1998). The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity. Blood, 92(8): 2766–2770

PMID

24 Khalid A S, Joyce C, O’Donoghue K (2013). Prevalence of subclinical and undiagnosed overt hypothyroidism in a pregnancy loss clinic. Ir Med J, 106(4): 107–110

PMID

25 Kovalevsky G, Gracia C R, Berlin J A, Sammel M D, Barnhart K T (2004). Evaluation of the association between hereditary thrombophilias and recurrent pregnancy loss: a meta-analysis. Arch Intern Med, 164(5): 558–563

PMID

26 López Ramírez Y, Vivenes M, Miller A, Pulido A, López Mora J, Arocha-Piñango C L, Marchi R (2006). Prevalence of the coagulation factor XIII polymorphism Val34Leu in women with recurrent miscarriage. Clin Chim Acta, 374(1-2): 69–74

PMID

27 Madjunkova S, Volk M, Peterlin B, Plaseska-Karanfilska D (2012). Detection of thrombophilic mutations related to spontaneous abortions by a multiplex SNaPshot method. Genet Test Mol Biomarkers, 16(4): 259–264

PMID

28 McCormack L J, Kain K, Catto A J, Kohler H P, Stickland M H, Grant P J (1998). Prevalence of FXIII V34L in populations with different cardiovascular risk. Thromb Haemost, 80(3): 523–524

PMID

29 Mikkola H, Syrjälä M, Rasi V, Vahtera E, Hämäläinen E, Peltonen L, Palotie A (1994). Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood, 84(2): 517–525

PMID

30 Muszbek L, Bagoly Z, Bereczky Z, Katona E ( 2008). The involvement of blood coagulation factor XIII in fibrinolysis and thrombosis. Cardiovasc Hematol Agents Med Chem, 6(3):190–205

31 Nelen W L, Blom H J, Steegers E A, den Heijer M, Eskes T K (2000). Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril, 74(6): 1196–1199

PMID

32 Ozdemir O, Yenicesu G I, Silan F, Köksal B, Atik S, Ozen F, Göl M, Cetin A (2012). Recurrent pregnancy loss and its relation to combined parental thrombophilic gene mutations. Genet Test Mol Biomarkers, 16(4): 279–286

PMID

33 Poursadegh Zonouzi A, Chaparzadeh N, Ghorbian S, Sadaghiani M M, Farzadi L, Ghasemzadeh A, Kafshdooz T, Sakhinia M, Sakhinia E (2013). The association between thrombophilic gene mutations and recurrent pregnancy loss. J Assist Reprod Genet, 30(10): 1353–1359

PMID

34 Rallidis L S, Politou M, Komporozos C, Panagiotakos D B, Belessi C I, Travlou A, Lekakis J, Kremastinos D T (2008). Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years. Thromb Haemost, 99(6): 1085–1089

PMID

35 Regan L, Rai R (2002). Thrombophilia and pregnancy loss. J Reprod Immunol, 55(1-2): 163–180

PMID

36 Sajadi S, Samiei S, Kheirandish M, Jalaifar A(2008). The association of FXIII Val34Leu polymorphism with thrombotic events in patients referring to Iranian Blood Transfusion Organization. Sci J Iran Blood Transfus Organ, 4 (4): 247–252

37 Suzuki K, Henke J, Iwata M, Henke L, Tsuji H, Fukunaga T, Ishimoto G, Szekelyi M, Ito S (1996). Novel polymorphisms and haplotypes in the human coagulation factor XIII A-subunit gene. Hum Genet, 98(4): 393–395

PMID

38 Yioti G G, Panagiotou O A, Vartholomatos G A, Kolaitis N I, Pappa C N, Evangelou E, Stefaniotou M I (2013). Genetic polymorphisms associated with retinal vein occlusion: a Greek case-control study and meta-analysis. Ophthalmic Genet, 34(3): 130–139PMID:23289804