Polymorphisms in folate and homocysteine metabolizing genes and chromosome damage in mothers of Down syndrome children

Fabio Coppedè, Renato Colognato, Alessia Bonelli, Guja Astrea, Stefania Bargagna, Gabriele Siciliano, Lucia Migliore

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We recently observed an association between combinations of polymorphisms in the methylenetetrahydrofolate reductase (MTHFR 677C > T or 1298A > C) and reduced folate carrier (RFC-1 80G > A) genes and the risk of a Down syndrome (DS) pregnancy in young Italian women. Others have observed an association between a methionine synthase (MTR 2756A > G) gene polymorphism and the risk of a DS offspring in Italy. Moreover, in a separate study, we observed an increased frequency of both binucleated micronucieated cells (BNMN) and chromosome malsegregation events in peripheral lymphocytes of mothers of DS individuals aged less than 35 years at conception (MDS) in respect to controls. The aim of the present study was to evaluate chromosome damage, measured by means of the micronucleus assay, in peripheral lymphocytes of a group of women (n = 34) who had a DS child in young age ( T and 1298A > C, RFC-1 80G > A and MTR 2756A > G polymorphisms. We observed an increased frequency of BNMN in the MDS group compared to the control group (17.13 ± 8.31‰ vs. 10.28 ± 4.53‰; P <0.001), and, in the general population, a correlation between years of age and BNMN frequency (P = 0.05). A significant correlation between the frequency of BNMN and the MTHFR 677C > T polymorphism (P = 0.038) was also found. Present results indicate that MDS are more prone to chromosome damage than control mothers; moreover the contribution of folate and homocysteine metabolizing gene polymorphisms seems to have an effect on the baseline frequency of BNMN lymphocytes.

Original languageEnglish
Pages (from-to)2006-2015
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Issue number17
Publication statusPublished - Sep 1 2007


  • Down syndrome
  • Folate and homocysteine metabolism
  • Gene polymorphisms
  • Micronuclei
  • MTR
  • RFC-1

ASJC Scopus subject areas

  • Genetics(clinical)


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