title: Polymorphisms in folate and homocysteine metabolizing genes and chromosome damage in mothers of Down syndrome children.
abstract: 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 per thousand vs. 10.28 +/- 4.53 per thousand; 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.
authors: Department of Neurosciences, University of Pisa, Pisa, Italy.
authors: Fabio
authors: F
authors: Coppedè
authors: Renato
authors: R
authors: Colognato
authors: Alessia
authors: A
authors: Bonelli
authors: Guja
authors: G
authors: Astrea
authors: Stefania
authors: S
authors: Bargagna
authors: Gabriele
authors: G
authors: Siciliano
authors: Lucia
authors: L
authors: Migliore
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000328:Adult; D004314:Down Syndrome / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D006710:Homocysteine / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D009035:Mothers; D011110:Polymorphism, Genetic
chemical_list: D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase