Association of +505A>G Polymorphism at TAFI Gene with Recurrent Miscarriage in Iranian Women

Document Type : Original Article


1 Biology Department, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran

2 Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Laboratory Hematology and Blood Banking Department, School of Allied Medical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran


Background: Recurrent miscarriage (RM) is one of the major problems of public health globally. The thrombin-activatable fibrinolysis inhibitor (TAFI) gene is a plasma zymogen that regulates both fibrinolysis and inflammation. Genetic variants within TAFI gene are presumed to be associated with development of RM. This case-control study aimed to investigate the association of TAFI +505A>G polymorphism with RM in Iranian women referred to Meybod Genetic Center.
Methods: Fifty women with RM (at least 2 miscarriages) and 50 healthy women with no history of miscarriage or other fertility complications were participated in this study. The TAFI +505A>G polymorphism was genotyped by allele specific PCR (AS-PCR) assay.
Results: The mean age of cases with RM and controls was 27.25 ± 4.31 and 28.42 ± 3.22 years, respectively. The frequency of GG genotype and G allele was 0.00% in patients and controls. There was no significant difference between RM cases and controls in terms of +505A>G genotypes and alleles.
Conclusion: This study results indicated that there was no significant relationship between the TAFI +505A>G polymorphism and RM risk in Iranian women. However, further rigorous, studies with a larger sample size and different ethnicity are necessary to confirm our findings.


1. El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G, Bouet PE. Recurrent pregnancy loss: Current perspectives. Int J Womens Health 2017; 9: 331-45.
2. Pokale YS, Khadke P. Risk of Recurrent Miscarriage in India and the Effect of Paternal Age and Maternal Age. IRA-International J Appl Sci 2016; 3(3): 459-68.
3. Chatzidimitriou M, Chatzidimitriou D, Mavridou M, Anetakis C, Chatzopoulou F, Lialiaris T, et al. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women. Int J Lab Hematol 2017; 39(6): 590-5.
4. Ewington LJ, Tewary S, Brosens JJ. New insights into the mechanisms underlying recurrent pregnancy loss. J Obstet Gynaecol Res 2019; 45(2): 258-65.
5. van Dijk MM, Kolte AM, Limpens J, Kirk E, Quenby S, van Wely M, et al. Recurrent pregnancy loss: Diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis. Hum Reprod Update 2020; 26(3): 356-67.
6. Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open 2018; 2018(2): hoy004.
7. Huang W, Zhou H, Pi L, Xu Y, Fu LY, Yang Y, et al. Association between the rs2288947 polymorphism of the lncRNA TINCR gene and the risk of recurrent miscarriage in a Southern Chinese population. J Clin Lab Anal 2019; 33(6): e22919.
8. Najafi K, Mehrjoo Z, Ardalani F, Ghaderi-Sohi S, Kariminejad A, Kariminejad R, et al. Identifying the causes of recurrent pregnancy loss in consanguineous couples using whole exome sequencing on the products of miscarriage with no chromosomal abnormalities. Sci Rep 2021; 11(1): 6952.
9. Mohtaram S, Sheikhha MH, Honarvar N, Sazegari A, Maraghechi N, Feizollahi Z, et al. An Association Study of the SLC19A1 Gene Polymorphisms/Haplotypes with Idiopathic Recurrent Pregnancy Loss in an Iranian Population. Genet Test Mol Biomarkers 2016; 20(5): 235-40.
10. Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod 2021; 36(5): 1213-29.
11. Ahangari N, Doosti M, Mousavifar N, Attaran M, Shahrokhzadeh S, Memarpour S, et al. Hereditary thrombophilia genetic variants in recurrent pregnancy loss. Arch Gynecol Obstet 2019; 300(3): 777-82.
12. Corbo RM, Ulizzi L, Piombo L, Scacchi R. Association of ACE I/D polymorphism and recurrent miscarriages in an Italian population with a pre-modern reproductive pattern. Ann Hum Biol 2011; 38(1): 102-5.
13. Bigdeli R, Younesi MR, Panahnejad E, Asgary V, Heidarzadeh S, Mazaheri H, et al. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population. Syst Biol Reprod Med 2018; 64(4): 274-82.
14. Hwang KR, Choi YM, Kim JJ, Lee SK, Yang KM, Paik EC, et al. Methylenetetrahydrofolate reductase polymorphisms and risk of recurrent pregnancy loss: A case-control study. J Korean Med Sci 2017; 32(12): 2029-34.
15. 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.
16. Colucci M, Semeraro N. Thrombin activatable fibrinolysis inhibitor: At the nexus of fibrinolysis and inflammation. Thromb Res 2012; 129(3): 314-9.
17. Sillen M, Declerck PJ. Thrombin activatable fibrinolysis inhibitor (TAFI): An updated narrative review. Int J Mol Sci 2021; 22(7): 3670.
18. Tokgoz S, Zamani AG, Durakbasi-Dursun HG, Yılmaz O, Ilhan N, Demirel S, et al. TAFI gene polymorphisms in patients with cerebral venous thrombosis. Acta Neurol Belg 2013; 113(3): 291-7.
19. Abulata NN, Shaheen IA, Osman OM, Hussein AM, El-Khayat WM. The prevalence of combined vascular endothelial growth factor, endothelial nitric oxide synthase and thrombin-activatable fibrinolysis inhibitor genetic polymorphisms among Egyptian patients with recurrent spontaneous abortion. J Obstet Gynaecol Res 2019; 45(6): 1106-13.
20. Khidri FF, Waryah YM, Ali FK, Shaikh H, Ujjan ID, Waryah AM. MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: A case control study. BMC Med Genet 2019; 20(1): 1-12.
21. Pruner I, Djordjevic V, Miljic P, Kovac M, Antonijevic N, Rakicevic L, et al. +1040 C/T polymorphism in coding region of thrombin-activatable fibrinolysis inhibitor gene and the risk of idiopathic recurrent fetal loss. Blood Coagul Fibrinolysis 2010; 21(7): 679-82.
22. Martnez-Zamora MA, Creus M, Tassies D, Reverter JC, Civico S, Carmona F, et al. Reduced plasma fibrinolytic potential in patients with recurrent implantation failure after IVF and embryo transfer. Hum Reprod 2011; 26(3): 510-6.
23. ElDanasori N, Abulata N, Shaheen IA, ElGendy AM, El-Khayat W. Thrombin-Activatable Fibrinolysis Inhibitor Gene Polymorphism (TAFI1040C/T) in Women With Recurrent Spontaneous Abortion. Clin Appl Thromb Hemost 2018; 24(3):532-5.
24. Masini S, Ticconi C, Gravina P, Tomassini M, Pietropolli A, Forte V, et al. Thrombin-activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss. Fertil Steril 2009; 92(2): 694-702.