Folate Metabolism Gene Polymorphisms MTHFR C677T and A1298C and Risk for Down Syndrome Offspring

Abstract

Abstract 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.