title: Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all birth defects. NSCL/P has a multifactorial etiology that includes both genetic and environmental factors. The IRF6 gene and three further susceptibility loci at 8q24, 10q25, and 17q22, which were identified by a recent genome-wide association scan (GWAS), are confirmed genetic risk factors for NSCL/P in patients of European descent.
  
  
  METHODS
  A case-control association study was performed to investigate whether these four risk loci contribute to NSCL/P in a Mesoamerican population using four single nucleotide polymorphisms to represent IRF6 and the three novel susceptibility loci. A total of 149 NSCL/P patients and 303 controls of Mayan origin were included.
  
  
  RESULTS
  Single marker analysis revealed a significant association between NSCL/P and risk variants in IRF6 and the 8q24 and 10q25 loci. In contrast to previous findings, the association at the 8q24 locus was driven solely by homozygote carriers of the risk allele. This suggests that this locus might act in a recessive manner in the Mayan population. No evidence for association was found at the 17q22 locus. This may have been attributable to the limited power of the sample.
  
  
  CONCLUSIONS
  These results suggest that IRF6 and the 10q25 and 8q24 loci confer a risk for the development of NSCL/P in persons of Mayan origin.
authors.affiliation: Department of Biochemistry and Molecular Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.
authors.forename: Augusto
authors.initials: A
authors.lastname: Rojas-Martinez
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Oscar
authors.initials: O
authors.lastname: Chacon-Camacho
authors.forename: Rafael B R
authors.initials: RB
authors.lastname: Leon-Cachon
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Munoz-Jimenez
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nowak
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.forename: Ruth
authors.initials: R
authors.lastname: Herberz
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.forename: Mario
authors.initials: M
authors.lastname: Paredes-Zenteno
authors.forename: Abelardo
authors.initials: A
authors.lastname: Arizpe-Cantú
authors.forename: Susanne
authors.initials: S
authors.lastname: Raeder
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.forename: Rocio
authors.initials: R
authors.lastname: Ortiz-Lopez
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
mesh_terms: D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D050835:Interferon Regulatory Factors / Q000235:genetics*; D012307:Risk Factors
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors