Association between MTHFR C677T polymorphism and congenital heart disease. A family-based meta-analysis

Congenital heart disease (CHD) is the most common type of birth defect. It is suspected that polymorphisms in folate metabolism are associated with an increased risk of CHD, but the conclusion remains unclear. Studies have reported that the MTHFR C677T polymorphism was associated with the development of structural congenital heart malformations. The objective of this study was to conduct a meta-analysis of available studies to identify common polymorphisms in the MTHFR gene in children with CHD and their mothers and to test for an association between genotype and disease. In all, 19 eligible studies comprising 4,219 cases and 20,123 controls were included in this meta-analysis. A significant association was found between the MTHFR C677T polymorphism and CHD risk (OR: 1.26; 95 % CI = 1.06-1.51; p = 0.009) with no strong evidence of heterogeneity (I(2) = 39 %) in the fetal analysis. In the maternal analysis, the MTHFR C677T polymorphism was significantly associated with CHD risk (OR = 1.52; 95 % CI =  1.09-2.11; p = 0.01) with significant heterogeneity (I(2) = 63 %).