Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for Down syndrome offspring: a meta-analysis

Objectives: MTHFR C677T and A1298C have been associated with the risk of having an infant with Down syndrome (DS), but results were conflicting. We performed this meta-analysis to derive a more precise estimation of the association between maternal MTHFR polymorphisms and DS. Study design: An electronic search of PubMed and Chinese Biomedicine database was conducted to select studies for meta-analysis. Twenty-eight case-control studies containing MTHFR C677T and A1298C gene polymorphisms were chosen, and odds ratio (OR) with confidence interval (CI) was used to assess the strength of this association. Results: Case-control studies including 2806 cases and 4597controls for MTHFR C677T were identified. The overall results suggested that the variant genotypes MTHFR C677T were associated with DS risk (TT+CT vs. CC: OR = 1.305, 95% CI: 0.125-1.514, p = 0). In the stratified analysis, individuals with the T-carriers genotype in the dominant model had increased risk of DS (OR = 1.171, 95% CI: 0.976-1.405, p = 0.09) in Caucasian subjects and in Asian subjects (OR = 1.749, 95% CI: 1.084-2.824, p = 0.022). In addition, case-control studies including 1854 cases and 2364 controls for MTHFR A1298C were chosen. Associations between MTHFR A1298C and the risk of having a child with DS were not found. A symmetric funnel plot, the Egger's test (p = 0.126) suggested a lack of publication bias. Conclusion: This meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk for DS offspring. (c) 2012 Elsevier Ireland Ltd. All rights reserved.