Background: As a key enzyme in folate metabolism, 5,10- methylenetetrahydrofolate reductase (MTHFR) regulates the homeostasis between DNA synthesis and methylation. Data on the association between the MTHFR C677T polymorphism and congenital heart disease (CHD) are conflicting.
Methods: To assess the relationship between the MTHFR 677TT genotype and the risk of CHD, we performed a metaanalysis, searching in Pubmed for studies on this topic published in the English language up to 1 December 2010. For each study, we calculated odds ratios (ORs) and 95% confidence intervals (CIs), assuming frequency of allele comparison, homozygote comparison, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs. Thirteen studies were included in the meta-analysis.
Results: The MTHFR T allele was associated with a borderline significantly increased risk of CHD in the frequency of allele comparison (T vs. C: OR = 1.160; 95% CI = 0.990- 1.359; p = 0.001 for heterogeneity). The MTHFR TT genotype was not associated with the risk of CHD in the homozygote comparison (TT vs. CC: OR = 1.272; 95% CI = 0.947-1.707; p = 0.028 for heterogeneity), the dominant genetic model (TT + CT vs. CC: OR = 1.127; 95% CI = 0.937-1.355; p = 0.034 for heterogeneity) and the recessive genetic model (TT vs. CTqCC: OR = 1.272; 95% CI = 0.975-1.659; p = 0.030 for heterogeneity). However, a stratification analysis showed that the association between the MTHFR C677T polymorphism and the risk of CHD was evident among Caucasians instead of Asians.
Conclusions: Our meta-analysis suggests that genotypes for the MTHFR C677T polymorphism might be associated with the risk of CHD among Caucasians.