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

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Abstract

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.

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Acknowledgments

This study was supported by Grants from Fundação de Auxílio à Pesquisa do Estado do Rio de Janeiro, Brazil (E-26/110.427/2011; E-26/102.797/2012), and Conselho Nacional de Desenvolvimento e Pesquisa, Brazil (476978/2008-4; 308885/2006-6; 573993/2008-4).

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Authors and Affiliations

  1. Departamento de Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Marcelo Aguiar Costa-Lima

  2. Departamento de Biologia Geral, Instituto de Biologia, Universidade Federal Fluminense, Rio de Janeiro, Brazil

    Márcia Rodrigues Amorim

  3. ECLAMC (Estudo Colaborativo Latino Americano de Malformações Congênitas) at Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Caixa Postal 68.011, Rio de Janeiro, 21944-970, Brazil

    Iêda Maria Orioli

  4. INAGEMP (Instituto Nacional de Genética Médica Populacional), Rio de Janeiro, Brazil

    Iêda Maria Orioli

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  1. Marcelo Aguiar Costa-Lima
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Correspondence to Iêda Maria Orioli.

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Costa-Lima, M.A., Amorim, M.R. & Orioli, I.M. Association of methylenetetrahydrofolate reductase gene 677C > T polymorphism and Down syndrome. Mol Biol Rep 40, 2115–2125 (2013). https://doi.org/10.1007/s11033-012-2270-z

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