How to Cite this Article: Brito LA, Bassi CFS, Masotti C, Malcher C, Rocha KM, Schlesinger D, Bueno DF, Cruz LA, Barbara LK, Bertola DR, Meyer D, Franco D, Alonso N, Passos-Bueno MR. 2012. IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population. Am J Med Genet Part A. 158A:2170–2175.
IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population†
Article first published online: 6 AUG 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 9, pages 2170–2175, September 2012
How to Cite
Brito, L. A., Bassi, C. F.S., Masotti, C., Malcher, C., Rocha, K. M., Schlesinger, D., Bueno, D. F., Cruz, L. A., Barbara, L. K., Bertola, D. R., Meyer, D., Franco, D., Alonso, N. and Passos-Bueno, M. R. (2012), IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population. Am. J. Med. Genet., 158A: 2170–2175. doi: 10.1002/ajmg.a.35526
- Issue published online: 24 AUG 2012
- Article first published online: 6 AUG 2012
- Manuscript Accepted: 20 MAY 2012
- Manuscript Received: 27 OCT 2011
- CNPq, FAPESP and the Brazilian Ministry of Health
- cleft lip/palate;
- IRF6 transcription levels;
- mesenchymal stem cell;
- structured association;
- common disease-common variant;
- admixture population;
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.