TY - JOUR
T1 - Polymorphisms in folate and homocysteine metabolizing genes and chromosome damage in mothers of Down syndrome children
AU - Coppedè, Fabio
AU - Colognato, Renato
AU - Bonelli, Alessia
AU - Astrea, Guja
AU - Bargagna, Stefania
AU - Siciliano, Gabriele
AU - Migliore, Lucia
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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.
AB - 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.
KW - Down syndrome
KW - Folate and homocysteine metabolism
KW - Gene polymorphisms
KW - Micronuclei
KW - MTHFR
KW - MTR
KW - RFC-1
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U2 - 10.1002/ajmg.a.31886
DO - 10.1002/ajmg.a.31886
M3 - Article
C2 - 17702010
AN - SCOPUS:34548312384
VL - 143
SP - 2006
EP - 2015
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 17
ER -