Association between 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and congenital heart disease: A meta-analysis

Abstract

BackgroundInconsistent results were reported in recent literature regarding the association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility of congenital heart disease (CHD). In this study, we performed a meta-analysis to investigate the associations by employing multiple analytical methods.MethodsLiterature search was performed and published articles were obtained from PubMed, Embase and CNKI databases based on the exclusion and inclusion criteria. Data were extracted from eligible studies and the crude odds ratios and their corresponding 95% confidence intervals (CIs) were calculated using random or fix effects model to evaluate the associations between the MTHFR C677T/A1298C polymorphisms and CHD development. Subgroup based analysis was performed by Hardy–Weinberg equilibrium, ethnicity, types of CHD, source of control and sample size.ResultsTwenty-four eligible studies were included in this meta-analysis. Significant association was found between fetal MTHFR C677T polymorphism and CHD development in all genetic models. The pooled ORs and 95% CIs in all genetic models indicated that MTHFR C677T polymorphism was significantly associated with CHD in Asian, but not Caucasian in subgroup analysis. The maternal MTHFR C677T polymorphism was not associated with CHD except for recessive model. Moreover, neither maternal nor fetal MTHFR A1298C polymorphism was associated with CHD.ConclusionThe fetal MTHFR C677T polymorphism may increase the susceptibility to CHD. Fetal MTHFR C677T polymorphism was more likely to affect Asian fetus than Caucasian. The MTHFR A1298C polymorphism may not be a risk of congenital heart disease.

A Targeted, Next-Generation Genetic Sequencing Study on Tetralogy of Fallot, Combined With Cleft Lip and Palate

“…16–21 Abnormal folate metabolism has been previously described as a possible risk factor for TOF. 6 It has been hypothesized that genetic polymorphisms in folate-metabolizing enzymes affect global DNA methylation as well as changes the synthesis and repair of DNA.…”

Meta-Prediction of MTHFR Gene Polymorphism and Air Pollution on the Risks of Congenital Heart Defects Worldwide: A Transgenerational Analysis

“…A total of 74 articles were excluded for not being the original studies, with 10 being meta-analyses [13,14,15,16,17,18,19,20,21,22]. We further excluded two articles that presented other congenital defects such as Down syndrome, and 33 articles without MTHFR genotype allele counts per groups.…”

“…In summary, previous meta-analyses published on MTHFR polymorphisms and CHD risk presented inconsistent results [13,14,15,16,17,18,19,20,21,22]. Additionally, no previous meta-analysis has been conducted to examine gene-environment interactions, specifically, the association of air pollution with MTHFR polymorphisms and the risks of CHD.…”

Advances in molecular genetics for pulmonary atresia

“…38 Therefore, polymorphisms in MTHFR may be closely related to the risk of CHD. 39 The relationship between MTHFR mutations and CHD is debatable, however. Verkleij-Hagoort et al 38 published a meta-analysis in 2007, concluding that the MTHFR variant c.677C > T on patient or maternal genotypes was not significantly associated with CHD.…”