Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: A meta-analysis

Cao, Yingli; Xu, Jianhua; Zhang, Zhaofeng; Huang, Xianliang; Zhang, Aiping; Wang, Jian; Zheng, Qiuling; Fu, Lingyuan; Du, Jing

doi:10.1016/j.gene.2012.10.091

Cited by 80 publications

(57 citation statements)

References 64 publications

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“…All these indicated C allele and AC?CC genotypes seem to be a risk factor of REPL. In our previous meta-analysis (Cao et al 2013), we found a significant association of MTHFR C677T polymorphism with RPL, which is supported by several studies (Nelen et al 1997;Unfried et al 2002;Nair et al 2012), In present study, we observed that MTHFR A1298C substitution increases the REPL risk. The inconsistent results between our previous meta-analysis and our present study may be attributed to the difference of gestational weeks used to define RPL in each study.…”

Section: Discussionsupporting

confidence: 89%

“…Many earlier studies described the relationship between MTHFR gene polymorphisms and RPL, but with conflict results (Cao et al 2013;Nair et al 2013). Recently, literatures firstly reported the association between other onecarbon metabolism genes methionine synthase reductase (MTRR) and solute carrier family 19, member 1 (SLC19A1) polymorphisms and RPL in other populations (Rah et al 2012;Kim et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

et al. 2014

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The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P \ 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P [ 0.05 (P = 0.093 and P = 0.084, respectively).

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

et al. 2014

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“…Indeed, a recent meta-analysis has found that there is no relation between MTHFR A1298C polymorphism and unexplained recurrent pregnancy loss. However, it has also been found that the MTHFR C677T type was a contributor for recurrent pregnancy loss but in East Asians only [12,13]. The debate on MTHFR gene polymorphism and unexplained RM remains elusive.…”

Section: Introductionmentioning

confidence: 99%

The impact of low molecular weight heparin on obstetric outcomes among unexplained recurrent miscarriages complicated with methylenetetrahydrofolate reductase gene polymorphism

et al. 2017

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Objectives:The association between methylenetetrahydrofolate reductase gene polymorphisms and unexplained recurrent miscarriage is elusive. The recommendations for improving pregnancy outcomes in these patients keep changing based on the available evidence. The aim of this study is to analyze the impact of low molecular weight heparin on obstetric outcomes of recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphism. Material and methods:We reviewed medical records of 121 patients with a history of recurrent miscarriage complicated by methylenetetrahydrofolate reductase gene polymorphisms, retrospectively. From among them, 68 patients were treated only with folic acid and iron. The remaining 53 patients were treated with folic acid, iron and prophylactic doses of low molecular weight heparin. The subsequent pregnancy outcomes of these patients were noted. Results:The live birth rate was higher in patients with anticoagulant therapy than in patients without anticoagulant therapy (48.5% vs. 69.8%, respectively, p: 0.015) and the congenital anomaly rate was lower in anticoagulant therapy group (17.6% vs. 3.8%, respectively, p: 0.022). The other obstetric outcomes were found to be similar between the two groups. Conclusions:The current study demonstrated that low molecular weight heparin improved the live birth rates among unexplained recurrent miscarriage patients complicated with methylenetetrahydrofolate reductase gene polymorphisms. However, the routine use of low molecular weight heparin did not improve the late pregnancy complications in these selected patients in the eastern region of our country. Further studies are needed to discriminate the effect of anticoagulation on the live birth rate of each of methylenetetrahydrofolate reductase gene polymorphism type.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Gonçalves¹,

Fraga²,

Santos³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Some cases of recurrent first trimester miscarriage have a thrombotic etiology. The aim of this study was to investigate the prevalence of the most common thrombophilic mutations -factor 2 R.O. Gonçalves et al. Genetics and Molecular Research 15 (3): gmr.15038156 V (FV) Leiden G1691A (FVL), prothrombin (FII) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T -in women with recurrent miscarriages. In this case-control study, we included 137 women with two or more consecutive first-trimester miscarriages (£12 weeks of gestation) and 100 healthy women with no history of pregnancy loss, and with at least one living child. DNA was extracted from the patient samples, and the relevant genes (FVL, FII, and MTHFR) were amplified by PCR, followed by restriction fragment length polymorphism, to assess the polymorphisms in these genes. The allelic frequencies of polymorphisms were not significantly different between the case and control groups. Polymorphisms in the MTHFR, FVL, and FII genes were not associated with recurrent miscarriage during the first trimester of pregnancy in Brazilian women (P = 0.479; P = 0.491 and P = 0.107, respectively). However, the etiologic identification of genetic factors is important for genetic counseling.

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Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: A meta-analysis

Cited by 80 publications

References 64 publications

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

The impact of low molecular weight heparin on obstetric outcomes among unexplained recurrent miscarriages complicated with methylenetetrahydrofolate reductase gene polymorphism

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

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