Meta Analysis of the Association betweenMTHFRC677T Polymorphism and the Risk of Congenital Heart Defects

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Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD). The aim of this study was to investigate the relationship of the MTHFR C677T polymorphism with the risk of CHD in children with CHD and their parents by meta-analysis. Studies were identified by searching electronic literature for papers before 2011, focusing on MTHFR C667T and the risk of CHD. All data were analyzed using the fixed effects model in Cochrane Review Manager 5.1.1. Twenty eligible case-control and family-based studies were included. Overall analysis yielded pooled odds ratios (OR) of 1.55 (95%CI 1.25–1.93), 1.84 (95%CI 1.23–2.74) and 1.20 (95%CI 0.94–1.54) for fetal, paternal and maternal MTHFR TT genotypes in case-control studies, respectively, but yielded a summarized OR of 0.9 (95%CI 0.97–1.12) in family-based studies. Our results suggested that the fetal and paternal MTHFR C667T gene may be associated with an increased occurrence of CHD. Further larger studies should be performed to investigate the interaction between maternal genetic polymorphism, folic acid intake and hyperhomocysteinemia, and the development of CHD.

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