title: Region 8q24 is a susceptibility locus for nonsyndromic oral clefting in Brazil.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate is a relatively common craniofacial defect with multifactorial inheritance. The association of the rs987525 single nucleotide variant, located in a gene desert at 8q24.21 region, has been consistently replicated in European populations. We performed a structured association approach combined with transcriptional analysis of the MYC gene to dissect the role of rs987525 in oral clefting susceptibility in the ethnically admixed Brazilian population.
  
  
  METHODS
  We performed the association study conditioned on the individual ancestry proportions in a sample of 563 patients and 336 controls, and in an independent sample of 221 patients and 261 controls. The correlation between rs987525 genotypes and MYC transcriptional levels in orbicularis oris muscle mesenchymal stem cells was also investigated in 42 patients and 4 controls.
  
  
  RESULTS
  We found a significant association in the larger sample (p = 0.0016; OR = 1.80 [95% confidence interval {CI}, 1.21-2.69], for heterozygous genotype, and 2.71 [95% CI, 1.47-4.96] for homozygous genotype). We did not find a significant correlation between rs987525 genotypes and MYC transcriptional levels (p = 0.14; r = -0.22, Spearman Correlation).
  
  
  CONCLUSIONS
  We present a positive association of rs987525 in the Brazilian population for the first time, and it is likely that the European contribution to our population is driving this association. We also cannot discard a role of rs987515 in MYC regulation, because this locus behaves as an expression quantitative locus of MYC in another tissue.
authors.affiliation: Human Genome Research Center, Institute of Biosciences, University of São Paulo, Brazil.
authors.forename: Luciano Abreu
authors.initials: LA
authors.lastname: Brito
authors.forename: Lívia Máris Ribeiro
authors.initials: LM
authors.lastname: Paranaiba
authors.forename: Camila Fernandes Silva
authors.initials: CF
authors.lastname: Bassi
authors.forename: Cibele
authors.initials: C
authors.lastname: Masotti
authors.forename: Carolina
authors.initials: C
authors.lastname: Malcher
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.forename: Katia Maria
authors.initials: KM
authors.lastname: Rocha
authors.forename: Lucas Alvizi
authors.initials: LA
authors.lastname: Cruz
authors.forename: Lígia Kobayashi
authors.initials: LK
authors.lastname: Bárbara
authors.forename: Nivaldo
authors.initials: N
authors.lastname: Alonso
authors.forename: Diogo
authors.initials: D
authors.lastname: Franco
authors.forename: Elizabete
authors.initials: E
authors.lastname: Bagordakis
authors.forename: Hercílio
authors.initials: H
authors.lastname: Martelli
authors.forename: Diogo
authors.initials: D
authors.lastname: Meyer
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
mesh_terms: D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics*; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D044469:Racial Groups; D014158:Transcription, Genetic
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc