Thrombophilia gene mutations in relation to recurrent miscarriage

Abstract

Background: Recurrent pregnancy loss is multifactorial involving clinical and biological risk factors. Evidence addressed the association of inherited thrombophilia with recurrent pregnancy loss and other serious pregnancy complications. However, the relation between thrombophilia associated gene mutations and adverse obstetric outcome is controversial and data in the literature are inconsistent. The aim of this study was to investigate the prevalence of thrombophilia associated gene mutations (factor V Leiden, prothrombin gene G20210A and methylene-tetrahydrofolate reductase MTHFR C677T) in relation to recurrent miscarriage.Methods: Case control study conducted on 200 women recruited from Elshatby Maternity Hospital clinics. The cases group included 100 women with history of three or more unexplained consecutive pregnancy losses, while 100 healthy age matched women with no history of recurrent miscarriages served as controls. Blood samples were collected from all women enrolled in the study for DNA extraction and genotype analysis. Factor V, prothrombin and MTHFR gene mutations were assayed based on polymerase chain reaction (PCR) and reverse-hybridization.Results: The prevalence of Factor V Leiden and prothrombin gene G20210A mutations did not differ significantly between cases and controls. However, MTHFR C667T mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls (p=0.001, p=0.003 respectively). The prevalence of combined thrombophilia of Factor V Leiden and MTHFR C677T was significantly increased in the patients group compared to controls (p=0.032). Regarding homozygosity of each of the gene mutations, no homozygosity was detected in controls and heterozygotes were significantly increased in the patients group compared to homozygotes.Conclusions: MTHFR mutations and the total prevalence of the three gene mutations were significantly increased in the patients group compared to controls. There was a significant increase in the prevalence of combined thrombophilia (Factor V Leiden and MTHFR C677T) in the patients group compared to controls without involvement of prothrombin gene.

Lack of Association between Factor V Leiden G1691A, Prothrombin G20210A, MTHFC677T Mutations, and Early Recurrent Pregnancy Loss in a Group of Sudanese Women

“…Other large prospective studies reported contradictory results stating that hypercoagulable thrombophilic gene mutations are not increased in women with recurrent miscarriage [16], [17]. In another study conducted by Henry et.al, [18], they confirmed the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population. They are also congruent with another study conducted by Abu-Asab et al, they did not find a significant association between FVL, FII, and MTHFR and RPL in the first and second trimester [19].…”

Is Homocysteine a Marker or a Risk Factor: A Question Still Waits for an Answer

“…This inherited deficiency lead to a 3.3-fold increase in the risk of miscarriage in a sample group of 185 Caucasian women [32,33]. Literature also specifies that associations between MTHFR C667T mutations to factor V Leiden and prothrombin gene mutations were identified in patients having recurrent miscarriages [34].…”

Deep Vein Thrombosis in Pregnancy and Postpartum: Are Sulfur-Containing Amino Acids Involved in Thrombophilia Condition?

“…Both points of view bring scientific arguments and, against the fact that the controversy continues, it is generally accepted that homocysteine is involved in vascular endothelial dysfunction and promotes thrombosis [41][42][43]. The literature mentions many diseases in which elevated homocysteine concentrations have been found in the blood: cardiovascular diseases [36,[44][45][46][47][48], neurological diseases [49][50][51][52], miscarriage [53][54][55], thrombophilia [56][57][58][59][60][61], bone fragility [62][63][64][65][66][67], diabetes [68][69][70][71][72][73][74], inflammation [75][76][77].…”

“…Clinical studies report that this mutation causes spontaneous abortions 3.3 times more frequently [53,54]. The particular case of the simultaneous mutation of MTHFR C667T, factor V Leiden, and/or prothrombin gene mutations will definitely cause recurrent pregnancy loss [55]. In addition to the thrombogenic effect, HHcy also manifests an effect of diminishing the fibrinolytic process.…”