title: Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for Down syndrome offspring: a meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk for DS offspring.
authors.affiliation: Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chan
authors.forename: Shuting
authors.initials: S
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Wenru
authors.initials: W
authors.lastname: Tang
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People; D016022:Case-Control Studies; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009035:Mothers; D011110:Polymorphism, Genetic; D044465:White People
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)