Genetic polymorphisms involved in folate metabolism and maternal risk for down syndrome: a meta-analysis

Dis Markers. 2014;2014:517504. doi: 10.1155/2014/517504. Epub 2014 Dec 4.


Inconclusive results of the association between genetic polymorphisms involved in folate metabolism and maternal risk for Down syndrome (DS) have been reported. Therefore, this meta-analysis was conducted. We searched electronic databases through May, 2014, for eligible studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association, which was estimated by fixed or random effects models. Heterogeneity among studies was evaluated using Q-test and I (2) statistic. Subgroup and sensitivity analyses were also conducted. Publication bias was estimated using Begg's and Egger's tests. A total of 17 case-controls studies were included. There was evidence for an association between the MTRR c.66A>G (rs1801394) polymorphism and maternal risk for DS. In the subgroup analysis, increased maternal risk for DS was found in Caucasians. Additionally, the polymorphic heterozygote MTHFD1 1958GA genotype was associated significantly with maternal risk for DS, when we limit the analysis by studies conformed to Hardy-Weinberg equilibrium. Finally, considering MTR c.2756A>G (rs1805087), TC2 c.776C>G (rs1801198), and CBS c.844ins68, no significant associations have been found, neither in the overall analyses nor in the stratified analyses by ethnicity. In conclusion, our meta-analysis suggested that the MTRR c.66A>G (rs1801394) polymorphism and MTHFD1 c.1958G>A (rs2236225) were associated with increased maternal risk for DS.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Down Syndrome / genetics*
  • Ferredoxin-NADP Reductase / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics*
  • Minor Histocompatibility Antigens
  • Polymorphism, Single Nucleotide


  • Minor Histocompatibility Antigens
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • MTHFD1 protein, human
  • Methylenetetrahydrofolate Dehydrogenase (NADP)