Analysis of Polymorphisms of Thrombophilia Genes as Risk Factor of Miscarriage: a cross-sectional descriptive study

Document Type : Original Article

Authors

1 PhD in Molecular Medicine, Department of Medical Epidemiology and Bio-informatics, Karolinska Institute, Stockholm, Sweden.

2 M.Sc. in Biology-Genetic, Saeed Pathobiology Laboratory, Tehran, Iran.

3 PhD in Medical Microbiology, Department of Molecular Biology, Research Center of Health Reference Laboratory, Ministry of Health and Medical Education, Tehran, Iran.

Abstract

Introduction: Thrombophilia genes are frequently reported to be major risk factors in the development of cardiovascular disease, thromboembolism and more importantly of pregnancy abortion. The study was conducted to investigate the prevalence rate of thrombophilia polymorphisms in Iranian women.
Methods: 591 women had miscarriage and infertility disorders who were referred to a private pathobiology laboratory in Tehran, Iran. The subjects were evaluated for single nucleotide polymorphisms using PCR-RFLP procedure during February 2013 to May 2016. Current method was validated and verified for specificity, sensitivity and accuracy by approved and known mutations controls and bioinformatics software’s.
ResultsAt present study, homozygosity of  prothrombin (AA), leiden (AA) and HPA-1 (TT) were not diagnosed. Among these genotypes, occurrence of FII (Wild type-GG and heterozygous-GA) was highest and lowest rate as 96.3% and 3.7%, respectively. The MTHFR 1298 A>C (AC and CC) had the highest frequency (296 subjects) comparison with the other ones. Outcomes frequency rates (%) of heterozygosity PAI-1, MTHFR1298, MTHFR677, Factor XIII, HPA-1, β-Fibrinogen, Factor V Leiden and Prothrombin were 72.6 %, 70%, 40.5%, 29.4%, 25.5%, 20%, 4.4% and 3.7%,  respectively.
Conclusion: Heterozygosity prevalence rate of PAI-1, MTHFR1298 and MTHFR677 are the most common in women. It would appear thrombophilia genes should be considered in preventive strategies particularly in coagulopathy and miscarriage disorders.

Keywords

References

  1. Elmahgoub IR, Afify RA, Abdel Aal AA, El-Sherbiny WS. Prevalence of coagulation factor XIII and plasminogen activator inhibitor-1 gene polymorphisms among Egyptian women suffering from unexplained primary recurrent miscarriage. J Reprod Immunol 2014; 103:18-22.
  2. Ticconi C, Mancinelli F, Gravina P, Federici G, Piccione E, Bernardini S. Beta-fibrinogen G-455A polymorphisms and recurrent miscarriage. Gyecol Obstet Invest 2011; 71(3):198-201.
  3. Hohlagschwandtner M, Unfried G, Heinze G, Huber JC, Nagele F, Tempfer C. Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage. Fertil Steril 2003; 79(5):1141-8.
  4. Ho WK. Deep vein thrombosis--risks and diagnosis. Aust Fam Physician 2010; 39(7):468-74.
  5. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107(23 Suppl): I9-16.
  6. De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 1996; 87(9):3531-44.
  7. Rosendaal FR, Reitsma PH. Genetics of venous thrombosis. J Thromb Haemost 2009; 7 Suppl:301-4.
  8. Neamatzadeh H, Ramazani V, Kalantar SM, Ebrahimi M, Sheikhha MH. Serum immune reactivity against β2- Glycoprotein-I and anti-neutrophil cytoplasmic autoantibodies by ELI-P-Complex screening technology in recurrent miscarriage. Minerva Ginecol 2016; 68(3):243-9.
  9. Valdez LL, Quintero A, Garcia E, Olivares N, Celis A, Rivas F Jr, et al. Thrombophilic polymorphisms in preterm delivery. Blood Cells Mol Dis 2004; 33(1):51-6.
  10. Yenicesu GI, Cetin M, Ozdemir O, Cetin A, Ozen F, Yenicesu C, et al. A prospective case-control study analyzes 12 thrombophilic gene mutations in Turkish couples with recurrent pregnancy loss. Am J Reprod Immunol 2010; 63(2):126-36.
  11. Proite MM, Malinverni AM, Oshima CT, Ishigai MM, Moron AF, et al. Mutations in the gene for factor v leiden and g20210a prothrombin polymorphism in women with recurrent spontaneous abortion: a retrospective study in a brazilian population. J Clin Gynecol Obstet 2016; 5(3):85-91.
  12. Hajia M. Secondary use of laboratory data: potentialities and limitations. Iran J Pathol 2019; 14(3):188-192.
  13. Hajia M, Safadel N, Samiee SM, Dahim P, Anjarani S, Nafisi N, et al. Quality assurance program for molecular medicine laboratories. Iran J Public Health 2013; 42(Supple1):119-124.
  14. Karimi A, Abdolhasani M, Hashemzadeh-Chaleshtori M, Pourgheysari B. A preliminary study of inherited thrombophilic risk factors in different clinical manifestations of venous thromboembolism in central Iran. Indian J Med Res 2015;142(1):46-52.
  15. Eskandari F, Akbari MT, Zare-Karizi Sh. Association of C677T and A1298C polymorphisms of the MTHFR gene with recurrent pregnancy loss. Pajouhandeh 2013; 18(4):167-173.
  16. Parand A, Honar N, Aflaki K, Imanieh MH, Haghighat M, Cohan N, et al. Management of bleeding in post-liver disease, surgery and biopsy in patients with high uncorrected international normalized ratio with prothrombin complex concentrate: an Iranian experience. Iran Red Crescent Med J 2013; 15(12):e12260.
  17. Farajzadeh M, Bargahi N, Poursadegh Zonouzi A, Farajzadeh D, Pouladi N. Polymorphisms in thrombophilic genes are associated with deep venous thromboembolism in an Iranian population. Meta Gene 2014; 15(2):505-513.
  18. Poursadegh Zonouzi A, Chaparzadeh N, Ghorbian S, Sadaghiani MM, Farzadi L, Ghasemzadeh A, et al. The association between thrombophilic gene mutations and recurrent pregnancy loss. J Assist Reprod Genet 2013; 30(10):1353-9.
  19. Kamali 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; 22(2):78-89.
  20. Sofi F, Lari B, Rogolino A, Marcucci R, Pratesi G, Dorigo W, et al. Thrombophilic risk factors for symptomatic peripheral arterial disease. J Vasc Surg 2005; 41(2): 255-60.
  21. Bargahi N, Farajzadeh M, Poursadegh-Zonouzi A, Farajzadeh D. Prevalence of thrombophilic gene polymorphisms in an Azari population of Iran. Hematol Rep 2014; 6(2):5321.
  22. Saidi S, Mahjoub T, Slamia LB, Ammou SB, Al-Subaie AM, Almawi WY. Polymorphisms of the human platelet alloantigens HPA-1, HPA-2, HPA-3, and HPA-4 in ischemic stroke. Am J Hematol 2008; 83(7):570-3.
  23. Khaniani MS, Afkhami F, Abbasalizadeh F, Mansoori Derakhshan S. Evaluation of thrombophilic genes in recurrent pregnancy loss: a case-control study in Iranian women. Int J Hum Genet 2016; 16(1):48-52.
  24. Ozturk N, Bakan E, Gul MA, Bakan N, Sebin E, Kiziltunc A. The frequency of some thrombophilic mutations in Eastern Turkey. Eurasian J Med 2016; 48(1):2-5.
  25. Bigdeli R, Younesi MR, Panahnejad E, Asgary V, Heidarzadeh S, Mazaheri H. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population. Syst Biol Reprod Med 2018; 64(4):274-282.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 23, Issue 4
June 2020
Pages 39-44

Files

Share

How to cite

Statistics