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The aim of our study was to evaluate the association between polymorphisms in the methylenetetrahydrofolate reductase ( MTHFR ) gene and the risk for congenital heart disease (CHD). Electronic literature databases were searched to identify eligible studies published before  Jun, 2014 . The association was assessed by the odds ratio (OR) with a 95% confidence interval (CI). The publication bias was explored using Begg's test. Sensitivity analysis was performed to evaluate the stability of the crude results. A total of 35 studies were included in this meta-analysis. For the  MTHFR  C677T polymorphism, we detected significant association in all genetic models for Asian children and the maternal population. Significant association was also detected in T vs. C for a Caucasian paediatric population (OR = 1.163, 95% CI: 1.008–1.342) and in both T vs. C (OR = 1.125, 95% CI: 1.043–1.214) and the dominant model (OR = 1.216, 95% CI:b1.096–1.348) for a Caucasian maternal population. For the  MTHFR  A1298C polymorphism, the association was detected in CC vs. AC for the Caucasian paediatric population (OR = 1.484, 95% CI: 1.035–2.128). Our results support the  MTHFR  -677T allele as a susceptibility factor for CHD in the Asian maternal population and the -1298C allele as a risk factor in the Caucasian paediatric population.

Association Between MTHFR Polymorphisms and Congenital Heart Disease: A Meta-analysis based on 9,329 cases and 15,076 controls