The Prevalence of Inherited Thrombophilic Polymorphisms in Saudi Females with Recurrent Pregnancy Loss Confirmed using Different Screening Protocols of PCR Gihan E-H Gawish 1,2* 1 Molecular Genetics-Medical Biochemistry, College of Medicine, King Abdullah City for Female Students, Al-Imam Muhammad Ibn Saud University, Riyadh, Saudi Arabia 2 Biological and Medical Science, University of British Columbia, Vancouver, Canada * Corresponding author: Gihan E-H Gawish, M.Sc., Ph.D., Post Doc Fellow, Associate Professor of Medical Biochemistry and Molecular Genetics Head of Biochemistry Department (Female Section), Director of Pre-Clinical Years (Female Section), College of Medicine, Al-Imam Muhammad Ibn Saud University, Riyadh, 11159, Saudi Arabia, E-mail: gagawish@imamu.edu.sa Received date: October 21, 2014, Accepted date: February 03, 2015, Published date: February 10, 2015 Copyright: © 2015 Gawish G E-H. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Inherited thrombophilia has recently been identified as a major cause of thrombembolism, but it may also contribute to adverse pregnancy outcomes and recurrent pregnancy loss. Three gene mutations namely leiden (FV G1691A), prothrombin (FII G20210A), and methylenetetrahydrofolate reductase (MTHFR C677T) are the most common types of hereditary thrombophilias in women with RPL, which in turn can result in placentation. These are usually undiagnosed, because most carriers are asymptomatic. The aim of this study was to determine the association of specific inherited thrombophilias and recurrent pregnant loss (RPL) among Saudi women. The study included 142 females were 72 had a history of 2 or more events of fetal loss in any of the 3 trimesters of pregnancy. The remaining 70 were clinically healthy women with a good obstetric history and have designated as a control group. Detection of inherited thrombophilia genes mutations was confirmed using different PCR screening protocols. The frequencies of FV & FII mutations related to the pregnancy loss stages showed that FV mutation ratio was similar among cases with early or late stage pregnancy loss (25% - 26%) but significantly higher than that of controls (1.4%). On the other hand FII mutation ratio was high among cases with late pregnancy loss (50%) followed by early pregnancy loss (38%) and was significant higher than that of controls (1.4%). MTHFR C677T mutation was more common in group of women with fetal loss in first trimester compared to the controls. We have reported that the combinations of two or more thrombophilic polymorphism risk factors were observed in 10.8% healthy Saudi women with unexplained RPL while no more than one risk factor was observed in any of the controls. We concluded that there is a strong association between the combined inherited thrombophilic mutations related to FV G1691A, FII G20210A, and MTHFR C677T genes among Saudi women. Our data confirm the hypothesis that inherited thrombophilia is indeed a significant abnormality in the RPL subjects. Keywords: Recurrent pregnancy loss; Thrombophilias; Prothrombin; Leiden; Methylenetetrahydrofolate reductase Introduction Recurrent pregnancy loss is a common health problem among Saudi women at the reproductive age. It is a heterogeneous condition with three or more successive losses affecting 1-2% and two or more successive losses affecting up to 5% of women. Recently, thrombophilias have been suggested as a possible cause of RPL [1]. Although thrombophilia is considered controversial, a common cause in women with unexplained recurrent pregnancy loss, with prevalence as high as 65% in selected populations [2,3]. The guideline of American College of Obstetricians and Gynecologists in Sept. 2013 records that the inherited thrombophilias in pregnancy are protein C deficiency, protein S deficiency, antithrombin deficiency, FV G1691 A, prothrombin G20210A and MTHFR C677T. On the other hand, FV G1691 A, prothrombin G20210A and MTHFR C677T are the most common causes have been implicated as risk factors of hereditary thrombophilias in women with RPL which in turn can result in placentation [4]. The three most common genetic thrombophilias known to predispose to venous thrombosis are: FV (factor V Leiden), methylenetetrahydrofolate reductase mutation (MTHFR, C677T) [5,6], and FII (prothrombin G20210) (Figure 1) [7]. In FV, arginine is substituted by glutamine at amino acid residue 506 in coagulation FV [8]. Due to this substitution, FV becomes resistant to degradation by activated protein C, increasing the risk of venous thromboembolism 3–5-fold in heterozygous individuals [9]. In FII G20210A, a G to A transition at position 20210 of the 3′ untranslated region of the FII gene has been found to be associated with increased prothrombin levels and a 3-fold increased risk for venous thrombosis in heterozygotes [10]. The homozygous state for the C to T transition at position 677 of MTHFR gene is associated with hyperhomocysteinaemia which predisposes to thrombosis [11]. The FV mutation is the most studied inherited thrombophilia in relation to pregnancy complications. FV is a genetic disorder was described as an underlying cause of APC (Anti Protein C) resistance. This mutation involves a guanine to adenine substitution (FV Arg506Gln) (G-to-A) at nucleotide 1691 in exon 10, which results in synthesis of a defective Leiden molecule (FV), resistant to cleavage by APC, [8-11]. Gawish, J Mol Genet Med 2015, 9:1 DOI: 10.4172/1747-0862.1000156 Research Article Open Access J Mol Genet Med ISSN:1747-0862 JMGM, an open access journal Volume 9 • Issue 1 • 1000156 J o u r n a l o f M o l e c u l a r a n d G e n e t i c M e d i c i n e ISSN: 1747-0862 Journal of Molecular and Genetic Medicine