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

Eur J Obstet Gynecol Reprod Biol. 2013 Apr;167(2):154-9. doi: 10.1016/j.ejogrb.2012.11.022. Epub 2013 Jan 5.

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.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Asian People
  • Case-Control Studies
  • Down Syndrome / genetics*
  • Down Syndrome / metabolism
  • Female
  • Genes, Dominant
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Models, Genetic
  • Mothers*
  • Polymorphism, Genetic*
  • White People

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)