Document Type : Original Article


1 Scientific-Applied Training Center of Farzanegan Andishmand Massoud (FAM), Tehran, Iran

2 Shafa nevroscience research center, khatam Alanbia Hospital, Tehran, Iran

3 Department of Biology, Islamic Azad University, Parand Branch, Tehran, Iran


Introduction and Aim: According to the WHO definition, recurrent miscarriage is a consecutive pregnancy loss before weeks 22. Different factors involved in recurrent abortion as a multifactorial disease. Genetic factors are one of the important factors associated with recurrent abortion. VEGFA (Vascular Endothelial Growth Factor A) is one of the important gene in angiogenesis. MTHFD1 (Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase, And Formyltetrahydrofolate Synthetase 1) is a protein-coding gene that metabolism folate. The goal of this article is to assess the association between single nucleotide polymorphisms of VEGFA and MTHFD1 and the recurrent miscarriage in Iranian women.
Material and method: The study group was 50 women with recurrent miscarriages and the control groups consisted of 10 women with at least two successful pregnancies and no miscarriages. The DNA extracted from leucocytes cells. PCR was used to find the association between VEGFA and MTHFD1 genes and recurrent miscarriages. Analyzing performed with FinchTV software after data sequencing.
Result: Our results showed that the polymorphism frequency of CC and CT in rs2236225 VEGFA were 86% and 14% in women with recurrent miscarriages and 90% and 10% in the control group. the polymorphism frequency of GG and GA in rs3025039MTHFD1 were 82% and 18% in women with recurrent miscarriages and no polymorphism was detected in the control group.
Conclusion: These results showed that there is an association between single nucleotide polymorphisms of VEGFA and MTHFD1 and the recurrent miscarriage in Iranian women. Furthermore, MTHFD1 polymorphism could be a molecular marker in the diagnosis of recurrent miscarriage.


Main Subjects

Aggarwal, S., Parveen, F., Faridi, R.M., Phadke, S., Borkar, M. and Agrawal, S. 2011. Vascular endothelial growth factor gene polymorphisms in north indian patients with recurrent miscarriages. Reproductive biomedicine online, 22(1): 59-64.
Casillas, S. and Barbadilla, A. 2017. Molecular population genetics. Genetics, 205(3): 1003-1035.
Eller, A.G., Branch, D.W., Nelson, L., Porter, T.F. and Silver, R.M. 2011. Vascular endothelial growth factor-a gene polymorphisms in women with recurrent pregnancy loss. Journal of reproductive immunology, 88(1): 48-52.
Ferrara, N., Gerber, H.-P. and LeCouter, J. 2003. The biology of vegf and its receptors. Nature medicine, 9(6): 669-676.
Ford, H.B. and Schust, D.J. 2009. Recurrent pregnancy loss: Etiology, diagnosis, and therapy. Reviews in obstetrics and gynecology, 2(2): 76.
Ghasemi, N., Dehghani Firouzabadi, R. and Ahmadi, S. 2017. Association of -460c/t and +405 g/c polymorphisms of vascular endothelial growth factor gene and susceptibility of ovarian hyperstimulation syndrome. International Journal of Reproductive BioMedicine, 15(2): 87-92.
He, D., Yu, Z., Liu, S., Dai, H., Xu, Q. and Li, F. 2018. Methylenetetrahydrofolate dehydrogenase 1 (mthfd1) is underexpressed in clear cell renal cell carcinoma tissue and transfection and overexpression in caki-1 cells inhibits cell proliferation and increases apoptosis. Medical science monitor: international medical journal of experimental and clinical research, 24: 8391.
Kamali, M., Hantoushzadeh, S., Borna, S., Neamatzadeh, H., Mazaheri, M., Noori-Shadkam, M. and Haghighi, F. 2018. Association between thrombophilic genes polymorphisms and recurrent pregnancy loss susceptibility in the iranian population: A systematic review and meta-analysis. Iranian biomedical journal, 22(2): 78.
Kim, Y.-J., Chul, W., Jun, K.-H. and Chin, H.-M. 2019. Genetic polymorphisms of vascular endothelial growth factor (vegf) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy. BMC cancer, 19(1): 483.
Li, L., Donghong, L., Shuguang, W., Hongbo, Z., Jing, Z. and Shengbin, L. 2013. Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage. The Journal of Maternal-Fetal & Neonatal Medicine, 26(7): 686-690.
Murthy, J., Gurramkonda, V.B. and Lakkakula, B.V. 2014. Significant association of mthfd1 1958g> a single nucleotide polymorphism with nonsyndromic cleft lip and palate in indian population. Medicina oral, patologia oral y cirugia bucal, 19(6): e616.
Papazoglou, D., Galazios, G., Papatheodorou, K., Liberis, V., Papanas, N., Maltezos, E. and Maroulis, G.B. 2005. Vascular endothelial growth factor gene polymorphisms and idiopathic recurrent pregnancy loss. Fertility and sterility, 83(4): 959-963.
Robinson, G.E. 2014. Pregnancy loss. Best practice & research Clinical obstetrics & gynaecology, 28(1): 169-178.
Şamlı, H., Demir, B., Özgöz, A., Atalay, M. and Uncu, G. 2012. Vascular endothelial growth factor gene 1154 g/a, 2578 c/a, 460 c/t, 936 c/t polymorphisms and association with recurrent pregnancy losses. Genet. Mol. Res., 11(4): 4739-4745.
Strachan, T., Goodship, J. and Chinnery, P. 2014. Genetics and genomics in medicine. Taylor & Francis.
Sutherland, H.G., Hermile, H., Sanche, R., Menon, S., Lea, R.A., Haupt, L.M. and Griffiths, L.R. 2014. Association study of mthfd 1 coding polymorphisms r 134 k and r 653 q with migraine susceptibility. Headache: The Journal of Head and Face Pain, 54(9): 1506-1514.
Vural, P., Küskü-Kiraz, Z., Doğru-Abbasoğlu, S., Çil, E., Karadağ, B., Akgül, C. and Uysal, M. 2009. Vascular endothelial growth factor− 2578 a/c,− 460 t/c and+ 405 g/c polymorphisms in polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology, 147(1): 57-60.
Wang, W., Jiao, X.-H., Wang, X.-P., Sun, X.-Y. and Dong, C. 2016. Mtr, mtrr, and mthfr gene polymorphisms and susceptibility to nonsyndromic cleft lip with or without cleft palate. Genetic Testing and Molecular Biomarkers, 20(6): 297-303.
Wolman, I. 2014. Berek and novak’s gynecology 15th edition. Springer.
Zheng, J., Lu, X., Liu, H., Zhao, P., Li, K. and Li, L. 2015. Mthfd1 polymorphism as maternal risk for neural tube defects: A meta-analysis. Neurological Sciences, 36(4): 607-616.