Association Between Methionine Synthase Reductase A66G Polymorphism and the Risk of Congenital Heart Defects: Evidence From Eight Case–Control Studies

Methionine synthase reductase (MTRR) plays a major role in hyperhomocysteinemia, a risk factor related to the occurrence of congenital heart defects (CHDs). However, the associations between MTRR polymorphism and CHDs have been inconclusive. Thus, a metaanalysis of eight case–control studies was conducted to investigate 3,592 cases and 3,638 control subjects for MTRR A66G polymorphism to identify the association. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. The results showed that MTRR A66G polymorphism was associated with a higher CHD risk in the allele comparison (G vs A: OR 1.163; 95 % CI 1.016–1.330; Pheterogeneity = 0.004), the homozygote comparison (GG vs AA: OR 1.332; 95 % CI 1.020–1.740; Pheterogeneity = 0.035), and the dominant model (GG/AG vs AA: OR 1.218; 95 % CI 1.001–1.482; Pheterogeneity = 0.001). In the subgroup analysis, this polymorphism was associated with CHDs in Asians in the homozygote comparison (GG vs AA: OR 1.427; 95 % CI 1.017–2.001; Pheterogeneity = 0.019) and the allele comparison (G vs A: OR 1.203; 95 % CI 1.018–1.422; Pheterogeneity = 0.002). In summary, the metaanalysis demonstrated that MTRR A66G polymorphism is a risk factor for CHDs. Further studies should be performed to investigate the association of plasma homocysteine levels, enzyme activity, parental genotypes, and vitamin complex intakes with the risk of CHDs.