Role of Prothrombin and Methylenetetrahydrofolate Reductase Gene Polymorphisms as well as Thrombophilia Markers, as Risk Factors for Unexplained Recurrent Miscarriage: A Case-Control Study

Abstract

Background: Unexplained recurrent miscarriage (RM) is still an unsolved reproductive health problem. Inheritedthrombophilias have been one of the causes. Mutation in genes encoding coagulation proteins, including prothrombin(PT G20210A) and methylenetetrahydrofolate reductase (MTHFR) genes, increase tendency for venous thromboembolism.This study aimed to evaluate association between polymorphisms in prothrombine and MTHFR genes withRM. We also evaluated association between protein C (PC), protein S (PS), antithrombin III (ATIII), and homocystienewith RM.Materials and Methods: We conducted a case-control study on women with history of miscarriages and healthycontrols. Genetic analysis was done using (TaqMan) polymerase chain reaction (PCR) technique and the othertests were performed to check general health indications and thrombophilia markers.Results: In this study, 195 RM group (group I) participants and 90 healthy controls (group II), PC, PS, ATIII deficiencyand Hyperhomocysteinemia were in 7.2, 65.6, 9.2, 10.8% of group I respectively, but was 1.1, 7.8, 2.2, 2.2% of groupII. PT G20210A showed two in group I were A/G, no A/G in group II, and no AA carrier in the either group. G allelewas observed in 99.5% of the group I and 100% of the group II, while A allele was detected in 0.5% of group I. MTHFRC677T gene showed C/T mutation in 33.3% of group I and 32.2% of group II, while T/T mutation was detected in 12.8%of group I and 8.9% of the group II. C allele was found in 70.5% of group I and 75% of group II, while T allele was foundin 29.5% of group I and 25% of group II (P=0.269).Conclusion: PT G20210A and MTHFR C677T gene mutations are not correlated with RM in the Egyptian population.However, Egyptian women with RM are strongly associated with hyperhomocysteinemia, PC, PS, and ATIII deficiencies(registration number: NCT03209063).

Keywords

• antithrombin iii
• protein c
• protein s
• recurrent miscarriage