ABSTRACT: Previous studies have focused on the association between polymorphisms of the genes involved in folate metabolism and Down syndrome (DS); however, the results remain inconclusive. The present meta-analysis was conducted to assess the association between RFC-1 A80G/MTR A2756G/CBS 844ins68 polymorphisms and the maternal risk of DS. Published studies were retrieved from PubMed, Embase, China National Knowledge Infrastructure and Chinese Biomedicine databases. Pooled odds ratios (ORs) with 95% confidence interval (CIs) were calculated using the fixed- or random-effects model. Additionally, test of heterogeneity, cumulative meta-analysis, sensitivity analysis and assessment of bias were also performed. Finally, 11, 11 and 6 studies were deemed eligible for meta-analyses of RFC-1 A80G, MTR A2756G and CBS 844ins68, respectively. A significant association between RFC-1 A80G polymorphism and DS risk was observed for G vs. A (OR=1.19, 95% CI: 1.004-1.40, P=0.04) and the recessive model (OR=1.28, 95% CI: 1.05-1.56, P=0.01). In the stratified analysis by source of control or sample size, a significantly increased risk was observed among hospital-based studies and large-sample groups (>200 subjects), respectively. In addition, the cumulative meta-analysis of the RFC-1 A80G variant revealed a trend toward an association as the amount of data increased. However, for the MTR A2756G and CBS 844ins68 polymorphisms, no obvious association was found for all genetic models. In summary, the present meta-analysis demonstrated that RFC-1 A80G, but not MTR A2756G or CBS 844ins68, was considered as a maternal risk factor for DS in the offspring.
