Folate Metabolism and Genetic Variant in Down Syndrome: A Meta-Analysis

Objectives: Studies investigating the association between gene polymorphisms involved in homocysteine/folate metabolism and Down syndrome (DS) have reported contradictory or inconclusive results. A meta- analysis of 25 studies on association between MTHFR and MTRR polymorphism and DS including 1, 934/2,081/ cases/controls for MTHFR C677T polymorphism, 1,404/1,632/ cases/control for MTHFR A1298C polymorphism and 859 /1,132/cases/ control for MTRR A66G polymorphism was carried out. Study design: Studies were identified by searching the PubMed database for relevant articles published. Case – control studies were chosen, and odds ratio (OR) with confidence interval (CI) were used to assess the strength of association. Results: The overall results suggested that the variant genotypes MTHFR C677T were associated with DS risk (homozygote, TT vs. CC: OR=2.991; 95% CI: 1.321-3.558; P=0.001 and co dominant model, CT vs. CC: OR=1.1616 (1.216-1.845; P=0.0001). The result of the variant genotypes MTHFR A1298C showed its association with the DS risk (homozygote, AA vs. CC: OR=1.428; 95% CI: 1.016-1.849; P=0.0067).In the stratified analysis, results obtained in variant genotype of MTHFR C677T A66G had increased risk of DS in Caucasian subjects in codominant and dominant model while the increased risk was found in dominant models for Brazilian and Asian subjects. Again, for MTHFR A1298C variant, increased risk was found in Caucasian subject in co-dominant, dominant and recessive models and in co-dominant model for Brazilian population. The results also show that in A66G variant of MTRR had increased risk of DS in both Caucasian and Brazilian subjects in dominant model. Conclusion: This meta-analysis supports the idea that MTHFR C677T and MTHFR A1298C genotype is associated with increased risk for DS.