title: BHMT G742A and MTHFD1 G1958A polymorphisms and Down syndrome risk in the Brazilian population.
abstract: BACKGROUND
  Mechanisms underlying meiotic nondisjunction are poorly understood. Attempts to elucidate the causes of Down syndrome (DS) have analyzed the relationship between polymorphism in folate metabolism and DS.
  
  
  OBJECTIVE
  The role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A and betaine-homocysteine methyltransferase (BHMT) G742A polymorphisms in DS risk was investigated.
  
  
  METHODS
  Blood samples were collected from a total of 86 DS mothers and from 161 control mothers. The investigation of the MTHFD1 G1958A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by real-time PCR for the BHMT G742A polymorphism.
  
  
  RESULTS
  The median maternal age of case mothers (30.40; 12.9-46.3 years) was significantly higher (p<0.0005) than in the control group (26.60; 15.4-57.9 years). The frequency of BHMT variant genotypes was significantly lower in DS mothers compared with controls (p=0.047). A significant decreased risk for BHMT 742 AA genotype (odds ratio [OR]=0.30; 95% confidence interval [CI]: 0.10-0.93; p=0.037) was observed. Moreover, when the dominant model was applied (BHMT 742GA or 7428AA versus 742GG), there was also a significant decrease in DS risk (OR=0.58; 95% CI: 0.37-0.98; p=0.042). MTHFD1 G1958A genotype frequencies were not significantly altered in DS mothers (p=0.206).
  
  
  CONCLUSIONS
  Our study suggests that the polymorphism BHMT G742A may modulate the DS risk in Brazilian mothers.
authors.affiliation: Department of Biologia Molecular, Faculdade de Medicina de São José do Rio Preto (FAMERP), Unidade de Pesquisa em Genética e Biologia Molecular (UPGEM), São José do Rio Preto, SP, Brazil.
authors.forename: Bruna Lancia
authors.initials: BL
authors.lastname: Zampieri
authors.forename: Joice Matos
authors.initials: JM
authors.lastname: Biselli
authors.forename: Eny Maria
authors.initials: EM
authors.lastname: Goloni-Bertollo
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Pavarino
mesh_terms: D000293:Adolescent; D000328:Adult; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics*; D001938:Brazil; D002648:Child; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008423:Maternal Age; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012306:Risk; D055815:Young Adult
chemical_list: D015778:Minor Histocompatibility Antigens; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase