The C677T Variant in the Methylenetetrahydrofolate Reductase Gene and Idiopathic Spontaneous Abortion in a Romanian Population Group

Abstract

Spontaneous abortions (SA) are a major public health problem and a frequent pregnancy associated disorder. Hereditary thrombophilia and hyperhomocysteinemia are considered to be important factors altering the placental circulation, the in utero development and the evolution of pregnancy. The MTHFR gene (methylenetetrahydrofolate reductase) exhibits an intensely studied polymorphism, C677T, that was repeatedly associated with hyperhomocysteinemia, increased thrombotic risk and was studied in relation with SA susceptibility. This study was aim to assessing the correlation of this polymorphism with idiopathic sporadic or recurrent SA in a Romanian population. In the case-control study, 131 patients with a history of SA and 135 women with no SA and at least one uneventful term delivery were included. The PCR-RFLP technique (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) was used to genotype the cases and controls and the results were analysed using the χ 2 test. The present analysis indicates that the MTHFR 677TT homozygous genotype is positively associated with recurrent idiopathic SA (OR 2.493, 95%CI 0.974, 6.379, p-value 0.06). This association was no longer observed in sporadic SA patients (OR 1.214, 95%CI 0.488, 3.017, p-value 0.814). In conclusion, the present study is consistent with previous reports which state that the presence of MTHFR 677T variant in homozygous status could represent a genetic susceptibility factor for recurrent idiopathic SA. Moreover, this is the first attempt to investigate this correlation in a Romanian group and to offer epidemiological support in estimating the frequencies of some common genetic variants in the Romanian population.

The Importance of Homozygous Polymorphisms of Methylenetetrahydrofolate Reductase Gene in Romanian Patients with Idiopathic Venous Thromboembolism

“…Several studies showed similar results to ours, regarding the prevalence of heterozygous MTHFR A1298C genotype in VTE: 36.9%, 37.4%, 37%, respectively (40,45,46). A higher frequency of heterozygotes was found in previous Romanian studies regarding thrombophilia in selected groups of patients: 50.1% and 47% in cases with bleeding in the first trimester of pregnancy and repetitive abortions, respectively (41,42). All of the mentioned studies from the literature show the preponderance of the heterozygous form of the MTHFR A1298C polymorphism versus the homozygous form and an absence of association with VTE.…”

“…26 (24,29,33,35,36) and a 20% increased risk of VTE (37), whereas other studies failed to reveal any significant association (25,(38)(39)(40). Previous Romanian studies regarding thrombophilia in obstetric cases detected frequencies of the homozygous MTHFR 677TT genotype of 19.4% and 19.56% in pregnant patients with haemorrhagic complications and in patients with repetitive spontaneous abortions; no significant associations were found, except for a slightly increased risk for repetitive abortions in the presence of this genotype (41,42). Our result regarding the prevalence of MTHFR 677TT in VTE cases is consistent with these studies.…”