title: Polymorphisms in FGF12, VCL, CX43 and VAX1 in Brazilian patients with nonsyndromic cleft lip with or without cleft palate.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common orofacial birth defect with a wide range prevalence among different populations. Previous association studies with populations from Europe and Asia have identified putative susceptibility markers for NSCL/P in fibroblast growth factor 12 (FGF12), vinculin (VCL), connexin 43 (CX43) and in a region close to the ventral anterior homeobox 1 (VAX1) gene. However, there have thus far been no studies of these markers in NSCL/P Brazilian patients, and as the genetic ancestry of the Brazilian population is highly varied, the predisposition to those disease markers can be different.
  
  
  METHODS
  Herein we conducted a structured association study conditioned on the individual ancestry proportions to determine the role of 16 polymorphic markers within those genes in 300 patients with NSCL/P and 385 unaffected controls.
  
  
  RESULTS
  None of the alleles and genotypes showed association with NSCL/P, though there was a significant association of the haplotype formed by VAX1 rs10787760, rs6585429 and rs1871345 polymorphisms with NSCL/P that did not persist Bonferroni correction for multiple tests.
  
  
  CONCLUSIONS
  Our results are consistent with a lack of involvement of FGF12, VCL and CX43 variants with NSCL/P pathogenesis in Brazilian patients. Furthermore, the higher frequency of a haplotype of VAX1 with NSCL/P patients suggests a low penetrant gene for oral cleft, and warrants further studies.
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: Ana Camila
authors.initials: AC
authors.lastname: Messetti
authors.forename: Elizabete
authors.initials: E
authors.lastname: Bagordakis
authors.forename: Hercílio
authors.initials: H
authors.lastname: Martelli-Júnior
authors.forename: Mario Sergio Oliveira
authors.initials: MS
authors.lastname: Swerts
authors.forename: Edgard
authors.initials: E
authors.lastname: Graner
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
mesh_terms: D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D002971:Cleft Lip / Q000150:complications / Q000235:genetics*; D002972:Cleft Palate / Q000150:complications / Q000235:genetics*; D018031:Connexin 43 / Q000235:genetics*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*; D016596:Vinculin / Q000235:genetics*
chemical_list: D018031:Connexin 43; C486356:FGF12 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; C572055:VAX1 protein, human; C488955:VCL protein, human; D016596:Vinculin; D005346:Fibroblast Growth Factors