Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil

J.M. Biselli, E.M. Goloni-Bertollo, B.L. Zampieri, R. Haddad, M.N. Eberlin, E.C. Pavarino-Bertelli
Published: January 22, 2008
Genet. Mol. Res. 7 (1) : 33-42
DOI: https://doi.org/10.4238/vol7-1gmr388

Cite this Article:
J.M. Biselli, E.M. Goloni-Bertollo, B.L. Zampieri, R. Haddad, M.N. Eberlin, E.C. Pavarino-Bertelli (2008). Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil. Genet. Mol. Res. 7(1): 33-42. https://doi.org/10.4238/vol7-1gmr388

About the Authors
J.M. Biselli, E.M. Goloni-Bertollo, B.L. Zampieri, R. Haddad, M.N. Eberlin, E.C. Pavarino-Bertelli

Corresponding author
E.C. Pavarino-Bertelli
E-mail: erika@famerp.br

ABSTRACT

The aim of the present study was to investigate the effect of polymorphisms C677T and A1298C in the methylenetetrahydrofolate reductase (MTHFR) gene, A2756G in methionine synthase reductase (MTR) gene and A80G in reduced folate carrier 1 (RFC1) gene, and plasma homocysteine (Hcy), on the maternal risk for Down syndrome (DS). Seventy-two DS mothers and 194 mothers who had no children with DS were evaluated. The investigation of the MTHFR C677TMTR A2756G and RFC1 A80G polymorphisms was performed by polymerase chain reaction and enzyme digestion and the MTHFR A1298C polymorphism by allele-specific polymerase chain reaction. Hcy quantification was carried out by liquid chromatography-tandem mass spectrometry. The median number of polymorphic alleles for the four loci tested was greater in DS mothers compared to the control group, and the presence of three or more polymorphic alleles increased the risk for having a child with DS 1.74 times. Elevated maternal risk for DS was also observed when plasma Hcy concentration was higher than 4.99 μmol/L. In conclusion, the presence of three or more polymorphic alleles for MTHFR C677T, MTHFR A1298C, MTR A2756G, and RFC1 A80G, and plasma Hcy concentrations higher than 4.99 μmol/L are maternal risk factors for DS.

Key words: Genetic polymorphism, Trisomy 21, Down syndrome, Nondisjunction,Trisomy 21.

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