The association of factor V Leiden mutation (G1691A) with pregnancy complications (miscarriage) in the Iran, East Azerbaijan
Year 2022,
Volume: 12 Issue: 2, 315 - 322, 30.06.2022
Selma Houjaghani
,
Abolfazl Ghorbani
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.
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
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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.
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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.
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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.
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T. Factor V Leiden as risk factor for unexplained stillbirth—a
population-based nested case-control study. Thromb Res.
2010;125(6):505-510.
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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.
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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.
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G, Jr. The relationship of the factor V Leiden mutation and
pregnancy outcomes for mother and fetus. Obstet Gynecol.
2005;106(3):517-524.
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Factor V Leiden mutation: a treatable etiology for sporadic and
recurrent pregnancy loss. Fertil Steril. 2008;89(2):410-416.
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differences in the prevalence of Factor V Leiden mutation
among patients on chronic warfarin therapy. Blood Cells Mol
Dis. 2006;37(2):100-106.
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thromboembolism in pregnancy and screening issues. Br J
Biomed Sci. 2004;61(3):157-164.
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factor V Leiden mutation and poor pregnancy outcomes
among Palestinian women. Thromb Res. 2010;126(2):e78-82.
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Methylenetetrahydrofolate reductase C677T polymorphism
and Factor V Leiden variant in Mexican women with
preeclampsia/eclampsia. Blood Cells Mol Dis. 2005;35(1):66-
69.
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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.
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Leiden mutation and pregnancy-related complications. Am J
Obstet Gynecol. 2010;203(5):469.e1-8.
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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
Year 2022,
Volume: 12 Issue: 2, 315 - 322, 30.06.2022
Selma Houjaghani
,
Abolfazl Ghorbani
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