Association of The Mthfr C677t, Factor V (Leiden) G1961a and Prothrombin G20210a Gene Mutations with Recurrent Spontaneous Aboration (Rsa) in Duhok Province
Genetic causes of thrombophilia have been suggested as a possible cause of recurrent pregnancy loss (RPL). Fifty female patients aged between 21- 40 years and experienced at least two times early pregnancy loss were enrolled in the current study. Blood samples were aspirated, infectious (TORCH), hormonal (gonadotrophines, steroids, and thyroid hormones), ultrasonic, and serological (anti-lupus and anti-phospholipid antibodies) evaluations were conducted to exclude any individual candidate who had been suspected to have causes of early pregnancy loss rather than the genetic attribute. DNA from each particular sample was extracted by components of (FVL-PTH and MTHFR)StripAssay®A kit Vienna Lab Diagnostics GmbH, Vienna, Austria).this kit includes three steps: (1) DNA isolation, (2) Multiplex PCR amplification was performed by using biotinylated primers, for detecting different mutations in the three genes of interest (FVL-PTH and MTHFR) (3) Hybridization of amplification products to a test strip containing allele-specific oligonucleotide probes immobilized as an array of parallel lines. The results revealed that 24 samples out of 50 had MTHFR C677T mutations while 2 samples only had FV (G1691A)mutation while prothrombin mutation (G20210A)has not been detected. In conclusion: genetic mutation had significant impact in patients suffered recurrent pregnancy loss.
Cramer, D.W. & Wise, L.A., (2000). The Epidemiology of Recurrent Pregnancy Loss.. Seminars in Reproductive Medicine., 18, pp.331-40.
Di Micco, P.; Di Fiore, R.; Niglio, A.; Quaranta, S.; Angiolillo, A. et al. (2008). Different outcome of six homozygotes for prothrombin A20210A gene variant. J. Transl. Med., 6, p.36.
Dong, Y.; Li, L. L.; Wang, R. X. et al. (2014). Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of chromosome abnormalities or polymorphisms. Genet. Mol. Res. (13): 2849-56.
Elgari, M. M.; Ibrahim, N. A.; Muddathir, A. R. M.; Eltoom, F. M.; Ibrahim, I. M. (2017). Frequency of Thrombophilic Gene Mutations in Patients with Deep Vein Thrombosis and in Women with Recurrent Pregnancy Loss. Open Life Sci., 12, pp.12-166.
Farahmand, K.; Totonchi, M.; Hashemi, M.; ReyhaniSabet, F.; Kalantari, H.; Gourabi, H.; MohseniMeybodi, A. (2015). Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. The journal of maternal-fetal and neonatal medicine. 29(8): 1269-1273.
Gazi, Y.; Ali, Y.; Pınar, Y.; Necdet, S.; Nilgün, T. (2012). Inherited thrombophilia with recurrent pregnancy loss in Turkish women – a real phenomenon? Ginekol. Pol. (83): 598-603.
Gonen, R.; Lavi, N.; Attias, D.; Schliamser, L.; Borochowitz, Z.; Toubi, E.; Ohel, G. (2005). Absence of association of inherited thrombophilia with unexplained third trimester intrauterine fetal death. Am. J. Obstet. Gynecol. 192 (3): 742-746.
Harris, E.N.; Gharavi, A.E.; Boey, M.L.; Patel, B.M.; Mackworth-Young, G.G.; Loizou, S. and Hughes, G.R. (1983). Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet. (11):1211.
Kobashi, G.; Kato, E. H.; Morikawa, M.; Shimada, S.; Ohta, K.; Fujimoto, S. et al (2005). MTHFR C677T Polymorphism and factor V leiden mutation are not associated with recurrent spontaneous abortion of unexplained etiology in Japanese women.. Semin Thromb. Hemost. , 31(3).
Kujovich, J.L. (2011). Factor V Leiden thrombophilia. Genet. Med. 13: 1-16.
Kutteh, W.H.; Park, V.M. & Deitcher, S.R.(1998). Hypercoagulable state mutation analysis in white patients with early first-trimester recurrent pregnancy loss.. Fertile. Steril.71: 1048-1053.
López-Jiménez, J.; Porras-Dorantes, Á.;Juárez-Vázquez, C.; García-Ortiz, J.; Fuentes-Chávez, C.; et al. (2016). Molecular thrombophilic profile in Mexican patients with idiopathic recurrent pregnancy loss. Genetics and molecular research. 15(4):
McPherson, E. (2016). Recurrence of stillbirth and second trimester pregnancy loss. American journal of medical genetics. 170A(5): 1174-1180.
Mierla, D.; Szmal, C.; Cretu, R.; Stoian, V.; Jordan, D. (2012). Association of Prothrombin (A20210G) and Factor V Leiden (A506G) with Recurrent Pregnancy Loss. Maedica. 7 :222-26.
Mtiraoui, N.; Zammiti, W.; Ghazouani, L.; Braham, N. J.; Saidi, S.; Finan, R. R. et al. (2006). MTHFR C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction. 131(2): 395-401.
Mukhopadhyay, R.; Saraswathy, K.N. & Ghosh, P.K.(2009). MTHFR C677T and Factor V Leiden in Recurrent Pregnancy Loss: A Study among an Endogamous Group in North India. Genetic Testing and Molecular Biomarkers. 13: 861-65.
Neamatzadeh, H.; Ramazani, V.; Kalantar, S. M.; Ebrahimi, M.; Sheikhha, M. H. (2016). Serum immune reactivity against β2Glycoprotein-I and anti-neutrophil cytoplasmic autoantibodies by ELI-P-Complex screening technology in recurrent miscarriage. Minerva ginecologica. 68(3): 243-249.
Sah, A. K.; Shrestha, N.; Joshi, P.; Lakha, R.; Shrestha, S.; Sharma, L.; Chandra, A.; et al. (2018). Association of parentalMethylene tetrahydro folatereductase (MTHFR) C677T gene polymorphism in couples with unexplained recurrent pregnancy loss. BMC Res Notes (2018) 11:233.
Sarig, G., Younis, J.S.; Hoffman, R.; Lanir, N.; Blumenfeld, Z.; Brenner, B. (2001). Thrombophilia Is Common in Women with Idiopathic Pregnancy Loss and Is Associated with Late Pregnancy Wastage. Fertility and Sterility. 77: 342-47.
Thiruchelvam, A and Sekaran, M. (2010). Thrombophilia abnormalities in recurrent pregnancy loss. Biomedical Research. 21 (1): 87-98.
Zahed, L. F.; Rayes, R. F.; Mahfouz, R. A.; Taher, A. T.; Maarouf, H. H.; Nassar, A. H. (2006). Prevalence of factor V Leiden, prothrombin and methylene tetrahydrofolatereductase mutations in women with adverse pregnancy outcomes in Lebanon. Am. J. Obstet. Gynecol. 195: 1114-1118.
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