title: DHFR 19-bp deletion and SHMT C1420T polymorphisms and metabolite concentrations of the folate pathway in individuals with Down syndrome.
abstract: BACKGROUND
  Down syndrome (DS) results from the presence and expression of three copies of the genes located on chromosome 21. Studies have shown that, in addition to overexpression of the Cystathionine β-synthase (CBS) gene, polymorphisms in genes involved in folate/homocysteine (Hcy) metabolism may also influence the concentrations of metabolites of this pathway.
  
  
  OBJECTIVE
  Investigate the association between Dihydrofolate reductase (DHFR) 19-base pair (bp) deletion and Serine hydroxymethyltransferase (SHMT) C1420T polymorphisms and serum folate and plasma Hcy and methylmalonic acid (MMA) concentrations in 85 individuals with DS.
  
  
  METHODS
  Molecular analysis of the DHFR 19-bp deletion and SHMT C1420T polymorphisms was performed by polymerase chain reaction (PCR) by difference in the size of fragments and real-time PCR allelic discrimination, respectively. Serum folate was quantified by chemiluminescence and plasma Hcy and MMA by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Individuals with DHFR DD/SHMT TT genotypes presented increased folate concentrations (p=0.004) and the DHFR II/SHMT TT genotypes were associated with increased MMA concentrations (p=0.008). In addition, the MMA concentrations were negatively associated with age (p=0.04).
  
  
  CONCLUSIONS
  There is an association between DHFR DD/SHMT TT and DHFR II/SHMT TT combined genotypes and folate and MMA concentrations in individuals with DS.
authors: Unidade de Pesquisa em Genética e Biologia Molecular, Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brasil.
authors: Cristiani Cortez
authors: CC
authors: Mendes
authors: Aline Maria Zanchetta de Aquino
authors: AM
authors: Raimundo
authors: Luciana Dutra
authors: LD
authors: Oliveira
authors: Bruna Lancia
authors: BL
authors: Zampieri
authors: Gustavo Henrique
authors: GH
authors: Marucci
authors: Joice Matos
authors: JM
authors: Biselli
authors: Eny Maria
authors: EM
authors: Goloni-Bertollo
authors: Marcos Nogueira
authors: MN
authors: Eberlin
authors: Renato
authors: R
authors: Haddad
authors: Maria Francesca
authors: MF
authors: Riccio
authors: Hélio
authors: H
authors: Vannucchi
authors: Valdemir Melechco
authors: VM
authors: Carvalho
authors: Érika Cristina
authors: ÉC
authors: Pavarino
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000097:blood / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007223:Infant; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood*; D011110:Polymorphism, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D012696:Glycine Hydroxymethyltransferase