MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta-analysis from 16 case-control studies

Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in the hyperhomocysteinemia, which is a risk factor related to the occurrence of congenital heart defect (CHD). However, the association between MTHFR polymorphism and CHD has been inconclusive.

We conducted an updated meta-analysis to provide comprehensive evidence on the role of MTHFR A1298C polymorphism in CHD. Databases were searched and a total of 16 studies containing 2207 cases and 2364 controls were included.

We detected that a significant association was found in the recessive model (CC vs. AA + AC: OR = 1.38, 95% CI: 1.10-1.73) for the overall population. Subgroup analysis showed that associations were found in patients without Down Syndrome in genetic models for CC vs. AA (OR = 1.47, 95% CI: 1.01-2.14), CC vs. AC (OR = 1.29, 95% CI: 1.00-1.66) and recessive model (OR = 1.44, 95% CI: 1.14-1.82). We conducted a meta-regression analysis, Galbraith plots and a sensitivity analysis to assess the sources of heterogeneity.

In summary, our present meta-analysis supports the MTHFR 1298C allele as a risk factor for CHD. However, further studies should be conducted to investigate the correlation of plasma homocysteine levels, enzyme activity, and periconceptional folic acid supplementation with the risk of CHD.