Premium
Polymorphisms in folate and homocysteine metabolizing genes and chromosome damage in mothers of Down syndrome children
Author(s) -
Coppedè Fabio,
Colognato Renato,
Bonelli Alessia,
Astrea Guja,
Bargagna Stefania,
Siciliano Gabriele,
Migliore Lucia
Publication year - 2007
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31886
Subject(s) - methylenetetrahydrofolate reductase , medicine , down syndrome , offspring , micronucleus , chromosome 21 , homocysteine , biology , genetics , population , endocrinology , micronucleus test , methionine synthase , pregnancy , chromosome , genotype , gene , methionine , toxicity , amino acid , environmental health
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 micronucleated 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 (<35 years) and in a control group (n = 35), and to correlate them with MTHFR 677C > 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. © 2007 Wiley‐Liss, Inc.