title: IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population.
abstract: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a complex disorder with a worldwide incidence estimated at 1:700. Among the putative susceptibility loci, the IRF6 gene and a region at 8q24.21 have been corroborated in different populations. To test the role of IRF6 in NSCL/P predisposition in the Brazilian population, we conducted a structured association study with the SNPs rs642961 and rs590223, respectively, located at 5' and 3' of the IRF6 gene and not in strong linkage disequilibrium (LD), in patients from five different Brazilian locations. We also evaluated the effect of these SNPs in IRF6 expression in mesenchymal stem cells (MSC). We observed association between rs642961 and cleft lip only (CLO) (P=0.009; odds ratio (OR) for AA genotype=1.83 [95% Confidence interval (CI), 0.64-5.31]; OR for AG genotype=1.72 [95% CI, 1.03-2.84]). This association seems to be driven by the affected patients from Barbalha, a location which presents the highest heritability estimate (H2=0.85), and the A allele at rs642961 is acting through a dominant model. No association was detected for the SNP rs590223. We did not find any correlation between expression levels and genotypes of the two loci, and it is possible that these SNPs have a functional role in some specific period of embryogenesis.
authors.affiliation: Human Genome Research Center, Department of Genetics, Institute de Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Brito
authors.forename: Camila F S
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: Kátia M
authors.initials: KM
authors.lastname: Rocha
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Bueno
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Cruz
authors.forename: Ligia K
authors.initials: LK
authors.lastname: Barbara
authors.forename: Débora R
authors.initials: DR
authors.lastname: Bertola
authors.forename: Diogo
authors.initials: D
authors.lastname: Meyer
authors.forename: Diogo
authors.initials: D
authors.lastname: Franco
authors.forename: Nivaldo
authors.initials: N
authors.lastname: Alonso
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 / Q000453:epidemiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors