Thrombophilic Gene Mutation and Correlation to Recurrent Miscarriage: An Egyptian Study

Document Type : Original Article


The Department of Clinical & Chemical Pathology* and Obstetrics & Gynecology Department**, Faculty of Medicine, Cairo University


Abstract Background: The most common complication in pregnancy is spontaneous abortion. Recurrent pregnancy loss (RPL) is three or more consecutive pregnancy loss before the 25th week of gestation. Genetical, environmental, viral, endocrinal, hematological and anatomical reasons are assumed to have a role. In spite of the continuous advancement in discovering the major reasons for fetal miscarriage, it is still one of the most important medical challenges. Some researchers claim that thrombophilia plays a big role in placenta related problems, intrauterine complications, disruption in fetal circulation and miscarriage. Pregnancy is a hyper-coagulable state, so any disruption or increase in thrombotic factors will result in maternal deep venous thrombosis on one hand, and clot formation, as well as disruption of the fetal circulation on the other hand, hence miscarriage. Discovering important corre-lations between coagulation factors and RPL may, in turn, decrease the rate of miscarriage via the use of antithrombotic measures. Aim of Study: Is to determine the association between factor five (FV), factor two (FII), Methylenetetrahydrofolate reductase (MTHFR) 677, (MTHFR) 1298, Methionine synthase (MTR) 2756 and Methionine synthase reductase (MTRR) 66 polymorphisms and the unexplained RPL among Egyptian women in their child bearing period. Patients and Methods: In this research, fifty women of reproductive age (19-45 years) with history of at least 3 unexplained miscarriages until the 24 weeks of gestation were included as cases, while 50 age-matched females as controls. Screening coagulation factors are tested for pregnant women with recurrent abortion such as Protein C, Protein S, the IgG & IgM for both ACLA and Beta-1-Glycoprotein, antithrombin III and lupus anticoagulant. This research studied the most common thrombophilic genes such as FII (1691), FV (20210), MTHFR (677 & 1298), MTR 2756 and MTRR 66 and were analyzed for heterogenicity or homogeneity to determine their role if any in miscarriage. Results: Abnormalities of screening coagulation factors such as Anticardiolipin antibody (ACLA) (IgG & IgM), Beta-1-Glycoprotein (IgG & IgM), antithrombin (AT) III, lupus anticoagulant, protein C (PC) and protein S (PS) deficiencies when determined, they showed no statistical significance.
Similarly, polymorphisms of FII, FV and MTHFR 677 showed no significance difference. In contrast, other thrombophilic gene mutationssuch as MTR 2756, MTHFR 1298 & MTRR 66 showed significant difference. MTR 2756 polymorphism revealed significant difference for heterozygous G/A with p -value 0.005 [Odds Raio (OR) 4.0, 95%CI 1.5-10.4]. In comparison MTHFR 1298 as well as MTRR 66 showed high significant difference with p-value less than 0.001, with G allele increasing the risk for miscarriage. For instance, MTHFR 1298, combined G/A and G/G genotypes increases risk for RPL (OR7.7, 95%CI 2.8-20.8 and OR 16.0 95%CI 3.2-80.1 respectively). Similarly, MTRR 66 Odds ratio revealed that G allele increases risk (G/A OR 26.1, 95%CI 7.0-96.8 and G/G OR 57.0 95%CI 13.0-249.7). Therefore, MTHFR 1298 & MTRR 66 revealed the highest significant difference with percentage of polymorphisms among cases 70% and 92%, respectively. Thus, one can conclude that G allele of those genes could be considered as susceptibility marker of RPL in Egyptian women.