The association of factor V Leiden mutation (G1691A) with pregnancy complications (miscarriage) in the Iran, East Azerbaijan

Year 2022, , 315 - 322, 30.06.2022

Selma Houjaghani , Abolfazl Ghorbani

https://doi.org/10.33808/clinexphealthsci.742378

Abstract

Objective: The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. Resistance to anticoagulant activity of activated protein C (APC), often due to point mutations in Factor V gene. Leiden mutation is definitely associated with pregnancy complications. In this study, we have investigated association of factor V Leiden with recurrent miscarriage in Iranian patients.
Methods: 200 women included in this study: 100 women as patients group with 2 or consecutive unexplained miscarriage and 100 women as controls group with at least one childbirth and without any abortion or pregnancy complications. Genomic DNA extracted from peripheral blood of each person. Presence or absence of mutations in the factor V Leiden gene performed by factor V Leiden coagulation test, and to determine homozygous and heterozygous of the factor V Leiden mutation, used HRM techniques by PCR Factor V Leiden Kit.
Results: In this study, Chi-square analysis was significant relationship between mutant G1691A and recurrent pregnancy loss, and other environmental variables in the statistical analysis, gestational age and family history, statistically significant association with recurrent pregnancy loss.
Conclusions: The results of this study showed that Factor V Leiden mutation has an effective role in the risk of pregnancy complications and recurrent miscarriage. Factor V Leiden mutation frequency in various countries due to genetic differences and different geographic can prone to recurrent pregnancy loss, better management of patients and adoption of effective preventive methods.

Keywords

Recurrent pregnancy loss, miscarriage, Factor V Leiden, mutation, pregnancy

Thanks

I would like to thank my dear professor Dr. Abolfazl Ghorbani. And with sincere thanks to Dr. Arami and the respected supervisor, Mr. Hamed Bagheri and all the staff of Dr. Armi's laboratory who were sincerely by my side.

References

• [1] Dehkordi MA, Soleimani A, Haji-Gholami A, Vardanjani AK, Dehkordi SA. Association of Deficiency of Coagulation Factors (Prs, Prc, ATIII) and FVL Positivity with Preeclampsia and/or Eclampsia in Pregnant Women. Int J Hematol Oncol Stem Cell Res. 2014;8(4):5-11.
• [2] Finan RR, Tamim H, Ameen G, Sharida HE, Rashid M, Almawi WY. Prevalence of factor V G1691A (factor V-Leiden) and prothrombin G20210A gene mutations in a recurrent miscarriage population. Am J Hematol. 2002;71(4):300-305.
• [3] Hiltunen LM, Laivuori H, Rautanen A, Kaaja R, Kere J, Krusius T. Factor V Leiden as a risk factor for preterm birth—a population-based nested case-control study. J Thromb Haemost. 2011;9(1):71-78.
• [4] Hiltunen LM, Laivuori H, Rautanen A, Kaaja R, Kere J, Krusius T. Factor V Leiden as risk factor for unexplained stillbirth—a population-based nested case-control study. Thromb Res. 2010;125(6):505-510.
• [5] Franchini M, Montagnana M, Targher G, Veneri D, Zaffanello M, Salvagno GL. Interpatient phenotypic inconsistency in severe congenital hemophilia: a systematic review of the role of inherited thrombophilia. Semin Thromb Hemost. 2009;35(3):307-312.
• [6] Mahjoub T, Mtiraoui N, Tamim H, Hizem S, Finan RR, Nsiri B. 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. 2005;80(1):12-19.
• [7] Jeddi-Tehrani M, Torabi R, Mohammadzadeh A, Arefi S, Keramatipour M, Zeraati H. Investigating Association of Three Polymorphisms of Coagulation Factor XIII and Recurrent Pregnancy Loss. Am J Reprod Immunol. 2010;64(3):212-217.
• [8] Parand A, Zolghadri J, Nezam M, Afrasiabi A, Haghpanah S, Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red Crescent Med J. 2013;15(12):e13708.
• [9] Dizon-Townson D, Miller C, Sibai B, Spong CY, Thom E, Wendel G, Jr. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol. 2005;106(3):517-524.
• [10] 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):410-416.
• [11] Limdi NA, Beasley TM, Allison DB, Rivers CA, Acton RT. Racial differences in the prevalence of Factor V Leiden mutation among patients on chronic warfarin therapy. Blood Cells Mol Dis. 2006;37(2):100-106.
• [12] Harvey D, Lowe GM. Factor V Leiden: association with venous thromboembolism in pregnancy and screening issues. Br J Biomed Sci. 2004;61(3):157-164.
• [13] Hussein AS, Darwish H, Shelbayeh K. Association between factor V Leiden mutation and poor pregnancy outcomes among Palestinian women. Thromb Res. 2010;126(2):e78-82.
• [14] Dávalos IP, Moran MC, Martínez-Abundis E, GonzálezOrtiz M, Flores-Martínez SE, Machorro V, et al. Methylenetetrahydrofolate reductase C677T polymorphism and Factor V Leiden variant in Mexican women with preeclampsia/eclampsia. Blood Cells Mol Dis. 2005;35(1):66- 69.
• [15] Rodger MA, Betancourt MT, Clark P, Lindqvist PG, DizonTownson D, Said J. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and metaanalysis of prospective cohort studies. PLoS Med. 2010;7(6): 1-12, e1000292.
• [16] Kjellberg U, van Rooijen M, Bremme K, Hellgren M. Factor V Leiden mutation and pregnancy-related complications. Am J Obstet Gynecol. 2010;203(5):469.e1-8.
• [17] Clark P, Walker ID, Govan L, Wu O, Greer IA. The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on hemorrhagic and thrombotic pregnancy outcomes. Br J Haematol. 2008;140(2):236-240.
• [18] Howley HE, Walker M, Rodger MA. A systematic review of the association between factor V Leiden or prothrombin gene variant and intrauterine growth restriction. Am J Obstet Gynecol. 2005;192(3):694-708.
• [19] Dudding TE, Attia J. Maternal factor V Leiden and adverse pregnancy outcome: deciding whether or not to test. J Matern Fetal Neonatal Med. 2012;25(7):889-894.
• [20] Seremak-Mrozikiewicz A, Drews K, Wender-Ozegowska E, Mrozikiewicz PM. The significance of genetic polymorphisms of factor V Leiden and prothrombin in the preeclamptic Polish women. J Thromb Thrombolysis. 2010;30(1):97-104.
• [21] Rahimi Z, Vaisi-Raygani A, Mozafari H, Kharrazi H, Rezaei M, Nagel RL. Prevalence of factor V Leiden (G1691A) and prothrombin (G20210A) among Kurdish population from Western Iran. J Thromb Thrombolysis. 2008;25(3):280-283.
• [22] Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland Homocysteine Study. Qjm. 2006;99(5):289-298.
• [23] Karimi S, Yavarian M, Azinfar A, Rajaei M, Azizi Kootenaee M. Evaluation the frequency of factor V Leiden mutation in pregnant women with preeclampsia syndrome in an Iranian population. Iran J Reprod Med. 2012;10(1):59-66.
• [24] Dashti AA, Jadaon MM. Race differences in the prevalence of the factor V Leiden mutation in Kuwaiti nationals. Mol Biol Rep. 2011;38(6):3623-3628.
• [25] Said JM, Higgins JR, Moses EK, Walker SP, Monagle PT, Brennecke SP. Inherited thrombophilias and adverse pregnancy outcomes: a case-control study in an Australian population. Acta Obstet Gynecol Scand. 2012;91(2):250-295.
• [26] Paidas MJ, Han CS, Hossain N, Lockwood CJ. Inherited and acquired thrombophilia in obstetrics. Hemostasis and Thrombosis in Obstetrics and Gynecology. 2011:67-110.
• [27] Skrzypczak J, Rajewski M, Wirstlein P, Goździewicz T, Breborowicz G, Leszczyńska-Gorzelak B. Incidence of hereditary thrombophilia in women with pregnancy loss in multi-center studies in Poland. Ginekol Pol. 2012;83(5):330- 336.(Polish)
• [28] Kashif S, Kashif MA, Saeed A. The association of factor V leiden mutation with recurrent pregnancy loss. J Pak Med Assoc. 2015;65(11):1169-172.
• [29] Soteh H, Aliasgharian A, Jalali H, Nejati Fard S, Kosarian M, Karami H. Frequency of Factor V Leiden, Prothrombin G20210 and C667T Mutations in Methylenetetrahydrofolate Reductase in Patients with Beta and Intermediate Thalassemia Compared with Normal Subjects in Northern Iran. Journal of Mazandaran University of Medical Sciences. 2011;21(81):2-9