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Open Medicine

formerly Central European Journal of Medicine

Editor-in-Chief: Darzynkiewicz, Zbigniew

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Volume 4, Issue 4


Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome — meta-analysis

Igor Medica
  • Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia
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/ Ales Maver
  • Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia
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/ Goncalo Augusto
  • Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia
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/ Borut Peterlin
  • Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia
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Published Online: 2009-10-03 | DOI: https://doi.org/10.2478/s11536-009-0055-0


Folate metabolism deficiency has been related to increased occurrence of maternal non-disjunction resulting in trisomy 21. Several polymorphisms in genes coding for folate metabolism enzymes have been investigated for association with the maternal risk of Down syndrome (DS) yielding variable results. We performed a meta-analysis of case-control studies obtained through the PubMed database. The studies on polymorphisms in the MTHFR, MTRR, MTR, RFC1 and CBS genes were included. The summary OR demonstrated a statistically significant increased risk of giving birth to a child with DS in mothers carrying the mutant allele of the MTHFR/C677T gene polymorphism (both genetic models) and in mothers homozygous for the mutant allele of the MTRR/A66G polymorphism (recessive genetic model). Analyses of other polymorphisms, MTHFR/A1298C, MTR/A2756G, RFC1/A80G, and CBS/844ins68, resulted in borderline or no statistical significance. In conclusion, our meta-analysis showed the significance of genetic alterations in the folate metabolism genes in maternal susceptibility to DS offspring. Our results suggest that the importance of folate supplementation to women in reproductive age in prevention of non-disjunction be revised. Further genetic studies on a combined effect of multiple folate metabolism genes is recommended. Additionally, more thorough studies on the haplotype analyses of genes is recommended as well, especially in populations that have not yet been investigated thus far.

Keywords: Down syndrome; folate metabolism; genetic polymorphism; MTHFR gene; MTRR gene; MTR gene; RFC1 gene; CBS gene; meta-analysis

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About the article

Published Online: 2009-10-03

Published in Print: 2009-12-01

Citation Information: Open Medicine, Volume 4, Issue 4, Pages 395–408, ISSN (Online) 2391-5463, DOI: https://doi.org/10.2478/s11536-009-0055-0.

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© 2009 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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