Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Congenital heart defects; Meta-analysis; Methylenetetrahydrofolate reductase; Polymorphism; Risk factor.