title: MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian population.
abstract: BACKGROUND
  Polymorphisms within the MTHFR (rs2274976) and MTHFD1 (rs2236225) genes were previously associated with maternal susceptibility for having an offspring with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population. However, as the genotypes of the patients with NSCL/P were not evaluated, it is not clear whether the effects are associated with maternal or offspring genotypes. The aim of this study was to evaluate the association of rs2274976 and rs2236225 in the pathogenesis of NSCL/P.
  
  
  METHODS
  By using the TaqMan 5'-exonuclease allelic discrimination assay, the present study genotyped the rs2274976 and rs2236225 polymorphisms in 147 case-parent trios, 181 isolated samples of NSCL/P and 478 healthy controls of the Brazilian population. Transmission disequilibrium test and structured case-control analysis based on the individual ancestry proportions were performed.
  
  
  RESULTS
  The transmission disequilibrium test showed a significant overtransmission of the rs2274976 A allele (p = 0.004), but no preferential parent-of-origin transmission was detected. The structured case-control analysis supported those findings, revealing that the minor A allele of rs2274976 was significantly more frequent in NSCL/P group compared with control group (p = 0.001), yielding an odds ratio of 3.46 (95% confidence interval, 2.05-5.85). No association of rs2236225 polymorphism with NSCL/P was observed in both transmission disequilibrium test and case-control analysis.
  
  
  CONCLUSIONS
  The results of the study revealed that the presence of the rs2274976 A allele is a risk marker for the development of NSCL/P in the Brazilian population.
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Sibele Nascimento
authors.initials: SN
authors.lastname: de Aquino
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hoshi
authors.forename: Elizabete
authors.initials: E
authors.lastname: Bagordakis
authors.forename: Maria Giulia Rezende
authors.initials: MG
authors.lastname: Pucciarelli
authors.forename: Ana Camila
authors.initials: AC
authors.lastname: Messetti
authors.forename: Helenara
authors.initials: H
authors.lastname: Moreira
authors.forename: Andreia
authors.initials: A
authors.lastname: Bufalino
authors.forename: Andréa
authors.initials: A
authors.lastname: Borges
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Rangel
authors.forename: Luciano Abreu
authors.initials: LA
authors.lastname: Brito
authors.forename: Mario Sergio
authors.initials: MS
authors.lastname: Oliveira Swerts
authors.forename: Hercilio
authors.initials: H
authors.lastname: Martelli-Junior
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Line
authors.forename: Edgard
authors.initials: E
authors.lastname: Graner
authors.forename: Sílvia R A
authors.initials: SR
authors.lastname: Reis
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D002648:Child; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D005819:Genetic Markers; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: MTHFD1; MTHFR; folic acid; nonsyndromic cleft lip with or without cleft palate; polymorphism; susceptibility