Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

Author(s)

Biselli, J. M. ^[1] ; Zampieri, B. L. ^[1] ; Goloni-Bertollo, E. M. ^[1] ; Haddad, R. ^[2] ; Fonseca, M. F. R. ^[2] ; Eberlin, M. N. ^[2] ; Vannucchi, H. ^[3] ; Carvalho, V. M. ^[4] ; Pavarino, E. C. ^[1]

Affiliation

^[1] Fac Med Sao Jose do Rio Preto FAMERP, Dept Biol Mol, Unidade Pesquisa Genet Biol Mol UPGEM, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Estadual Campinas UNICAMP, Dept Quim, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Dept Clin Med, BR-14049 Ribeirao Preto, SP - Brazil

^[4] Inst Pesquisa Fleury, Sao Paulo - Brazil

• Document type: Journal article
• Source: MOLECULAR BIOLOGY REPORTS; v. 39, n. 10, p. 9277-9284, OCT 2012.
• Web of Science Citations: 11

Abstract

Individuals with Down syndrome (DS) carry three copies of the Cystathionine beta-synthase (C beta S) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21. (AU)

• FAPESP's process: 08/10932-0 - Genetic polymorphisms on folate metabolic pathway and susceptibility to chromosome 21 nondisjunction.
• Grantee: Erika Cristina Pavarino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 03/09931-5 - Development and study of functional and structured materials: a view from complexity
• Grantee: Marcos Nogueira Eberlin
• Support Opportunities: PRONEX Research - Thematic Grants