Molecular Biology Reports

, Volume 40, Issue 3, pp 2115–2125

Association of methylenetetrahydrofolate reductase gene 677C > T polymorphism and Down syndrome

  • Marcelo Aguiar Costa-Lima
  • Márcia Rodrigues Amorim
  • Iêda Maria Orioli

DOI: 10.1007/s11033-012-2270-z

Cite this article as:
Costa-Lima, M.A., Amorim, M.R. & Orioli, I.M. Mol Biol Rep (2013) 40: 2115. doi:10.1007/s11033-012-2270-z


The association between Down syndrome (DS) and maternal polymorphisms in genes encoding folic acid metabolizing enzymes remains a controversial issue. A meta-analysis was performed to evaluate the association of maternal MTHFR 677C > T polymorphism and the risk of having a child with DS. Case–control studies were screened from major literature databases. Twenty articles from 13 countries worldwide, with a total of 2,101 DS and 2,702 control mothers, attended the inclusion criteria. We found a 50 % increase for the association of maternal homozygous TT genotype and DS in both fixed (OR = 1.51; 95 % CI 1.22–1.87) and random effects models (OR 1.54; 95 % 1.15–2.05). Similarly, a significant pooled OR was found for the heterozygote CT, with an OR 1.26; 95 % CI 1.10–1.43 (fixed effects model) and OR 1.28; 95 % 1.08–1.51 (random effects model). As ultra-violet B solar radiation highly depends on latitude, and can promote, in less pigmented skin, intravascular folate photolysis, we stratified the analysis by latitude region, defining as Tropical (between 23.5° S and 23.5° N), Sub-Tropical (between 23.5° and 40° N and S), and Northern (≥40o N). Significant association was only found for Sub-Tropical area, both using fixed and random effect models. In conclusion, MTHFR 677C > T polymorphism is a moderate risk factor for DS for some populations, and populations located in Sub-Tropical region seem to be at greater risk. Latitude, ethnicity, skin pigmentation, and red blood cell folate are important variables to be considered in future studies.


Down syndrome risk MTHFR 677C > T Meta-analysis Latitude UVB Folate 

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Marcelo Aguiar Costa-Lima
    • 1
  • Márcia Rodrigues Amorim
    • 2
  • Iêda Maria Orioli
    • 3
    • 4
  1. 1.Departamento de Genética, Instituto de Biologia Roberto Alcântara GomesUniversidade do Estado do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Departamento de Biologia Geral, Instituto de BiologiaUniversidade Federal FluminenseRio de JaneiroBrazil
  3. 3.ECLAMC (Estudo Colaborativo Latino Americano de Malformações Congênitas) at Departamento de Genética, Instituto de BiologiaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  4. 4.INAGEMP (Instituto Nacional de Genética Médica Populacional)Rio de JaneiroBrazil

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