Abstract
BackgroundMethylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs.MethodsAn electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis.ResultsA significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls.ConclusionThe results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted.
Highlights
Neural tube defects (NTDs) are a group of severe congenital malformations with an average worldwide birth prevalence of 1 in 500 [1], occurring due to incomplete closure of the neural tube between days 22 and 26 during embryo development [2]
Maternal nutritional status is a key determinant of pregnancy outcome, and attention has been focused on folic acid, a water-soluble B vitamin that acts as a cofactor in one-carbon transfer reactions and plays a central role in DNA methylation, synthesis, and repair [3,4]
Study eligibility Potentially relevant reports were selected by searching Embase and PubMed using the main search terms ‘‘methylene-tetrahydrofolate reductase,’’ ‘‘Methylenetetrahydrofolate reductase (MTHFR),’’ and ‘‘neural tube defects,’’ ‘‘NTD’’
Summary
Neural tube defects (NTDs) are a group of severe congenital malformations with an average worldwide birth prevalence of 1 in 500 [1], occurring due to incomplete closure of the neural tube between days 22 and 26 (somite stage 10–12) during embryo development [2]. The cause of NTDs is still poorly understood, accumulated evidence has suggested that genetic and/or environmental factors may contribute to NTD aetiology Among these factors, maternal nutritional status is a key determinant of pregnancy outcome, and attention has been focused on folic acid, a water-soluble B vitamin that acts as a cofactor in one-carbon transfer reactions and plays a central role in DNA methylation, synthesis, and repair [3,4]. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair It is a possible risk factor in neural tube defects (NTDs). We performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs
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