Methylenetetrahydrofolate reductase C677T polymorphism and congenital heart disease: a meta-analysis

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.

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.

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.

Our meta-analysis suggests that genotypes for the MTHFR C677T polymorphism might be associated with the risk of CHD among Caucasians.