Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain

Abstract

Background : Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. Methods : Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. Results : No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. Conclusions: In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation.

Metabolism and gene polymorphisms of the folate pathway in Brazilian women with history of recurrent abortion

“…The linear correlation between folate and homocysteine levels indicates an involvement of the nutritional status among the studied group. This fact should be considered in that previous work has suggested an association between poor nutritional intake and recurrent miscarriage 6,22 . The finding of a possible role of the cystathionine beta synthetase gene in the fetal-loss group emphasizes a possible contribution of this and other molecules and nutritional status in the homocysteine metabolism and abortion.…”

“…However, Creus et al 6 and Pihusch et al 25 did not demonstrate such association. In our study, the frequency of genetic polymorphisms that encode enzymes involved in folate-and vitamin B12-dependent homocysteine metabolism, the MTHFR C677T and A1298C; MS A2756G and CBS 844ins68 insertion, did not show differences in a group of women with recurrent miscarriage and a control group.…”

“…In spite of that, the C677T thermolabile variant of the MTHFR is an important genetic determinant of tHcy metabolism. Individuals homozygous for the mutant T allele exhibit increase elevations of the amino acid in their blood in comparison with other genotypes only under conditions of lower folate status 6,23 . This shows that B-vitamin status modifies the relationship between the MTHFR C677T mutation and tHcy serum levels.…”

“…Two main factors affect homocysteine concentration in humans: diet, specially the intake of folate and vitamin B12, and polymorphism in genes which encode enzymes or transport proteins involved in the folate-and vitamin B12-dependent homocysteine metabolism 3,4 . The dietary intake of essential micronutrients determines the efficiency of homocysteine metabolism in general, and the reduction in the dietary intake of B complex vitamins such as folate, B6 and B12 leads to an increase in the levels of plasma homocysteine 5,6 . The MTHFR gene polymorphisms are commonly associated with hyperhomocysteinemia 7,8 .…”

Association between the thrombophilic polymorphisms MTHFR C677T, Factor V Leiden, and prothrombin G20210A and recurrent miscarriage in Brazilian women

“…The FV Leiden (FVL) and G20210A mutations in the FV and FII (prothrombin) genes are believed to lead to enhanced blood coagulation, while mutations in the methylene tetrahydrofolate reductase (MTHFR) gene results in an elevation in the homocysteine levels; both sets of mutations have been identified as risk factors for thrombosis (Cao et al, 2013;Creus et al, 2013;Cao et al, 2014). Thrombophilia is a major cause of spontaneous loss of the fetus during the early stages of pregnancy, and is associated with complications such as preeclampsia, intrauterine growth restriction, placental abruption, and stillbirth, during the late stages of pregnancy (Frosst et al, 1995;Kovalevsky et al, 2004;Kujovich, 2011).…”