• cleft lip/palate;
  • IRF6 transcription levels;
  • rs642961;
  • rs590223;
  • mesenchymal stem cell;
  • structured association;
  • common disease-common variant;
  • admixture population;
  • heritability


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. © 2012 Wiley Periodicals, Inc.