The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls

Mol Biol Rep. 2012 Aug;39(8):7957-63. doi: 10.1007/s11033-012-1641-9. Epub 2012 May 4.


The 677C>T polymorphism within methylenetetrahydrofolate reductase (MTHFR) gene is related to an elevated level of homocysteine. Thus it may be considered as a genetic risk factor in ischemic stroke. Apparently studies of this type of polymorphism in childhood stroke have shown conflicting results. We performed meta-analysis of all the data that are available in relation with MTHFR polymorphism and the risk of ischemic stroke in children. We searched PubMed (last search dated December 2010) using "MTHFR polymorphism", "ischemic stroke" "child", "children", "pediatric stroke" as keywords and reference lists of studies and reviews on the topic. Finally, 15 case-control studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 822 children and adolescents after ischemic stroke and 1,552 control subjects. Fixed or random effects models were used depending on the heterogeneity between the studies. The association between ischemic stroke and 677C>T polymorphism within MTHFR gene was observed in three of the studies. The pooled analysis showed that TT genotype of MTHFR gene is more common in stroke patients than in controls (p = 0.0402, odds ratio = 1.57, 95 % confidence interval 1.02-2.41). The Egger's test did not reveal presence of a publication bias. The results based on a sizeable group of cases and controls have proved that the 677C>T polymorphism in MTHFR gene is associated with the development of ischemic stroke in children.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Brain Ischemia / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Infant
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Stroke / genetics*


  • Methylenetetrahydrofolate Reductase (NADPH2)