Folate gene polymorphisms and the risk of Down syndrome pregnancies in young Italian women

Fabio Coppedè, Giulia Marini, Stefania Bargagna, Liborio Stuppia, Fabrizio Minichilli, Ilaria Fontana, Renato Colognato, Guia Astrea, Giandomenico Palka, Lucia Migliore

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Maternal impairments in folate metabolism and elevated homocysteinemia are known risk factors for having a child with Down syndrome (DS) at a young age. The 80G>A polymorphism of the reduced folate carrier gene (RFC-1) has been recently demonstrated to affect plasma folate and homocysteine levels, alone or in combination with the 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. We performed the present study on 80 Italian mothers of DS individuals, aged less than 35 at conception, and 111 Italian control mothers, to study the role of the RFC-1 S0G>A, MTHFR 677C>T, and MTHFR 1298A>C genotypes to the risk of a DS offspring at a young maternal age. When polymorphisms were considered alone, both allele and genotype frequencies did not significantly differ between DS mothers and control mothers. However, the combined MTHFR677TT/RFC-1 80GG genotype was borderline associated with an increased risk (OR 6 (CI 95%: 1.0-35.9), P = 0.05), and to be MTHP1298AA/RFC-1 80(GA or AA) was inversely associated with the risk (OR 0.36 (CI 95%: 0.14-0.96), P = 0.04). Present results seem to indicate that none of the RFC-1 80G>A, MTHFR 677C>T, and MTHFR 1298A>C polymorphisms is an independent risk factor for a DS offspring at a young maternal age; however, a role for the combined MTHFR/RFC-1 genotypes in the risk of DS pregnancies among young Italian women cannot be excluded.

Original languageEnglish
Pages (from-to)1083-1091
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume140 A
Issue number10
Publication statusPublished - May 15 2006


  • Down syndrome
  • Folate gene polymorphisms
  • Folate metabolism
  • RFC-1
  • Risk of DS

ASJC Scopus subject areas

  • Genetics(clinical)


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