IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian 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 predispo...

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Published in:	American journal of medical genetics. Part A Vol. 158A; no. 9; pp. 2170 - 2175
Main Authors:	Brito, Luciano A., Bassi, Camila F.S., Masotti, Cibele, Malcher, Carolina, Rocha, Kátia M., Schlesinger, David, Bueno, Daniela F., Cruz, Lucas A., Barbara, Ligia K., Bertola, Débora R., Meyer, Diogo, Franco, Diogo, Alonso, Nivaldo, Passos-Bueno, Maria Rita
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-09-2012 Wiley-Liss Wiley Subscription Services, Inc
Subjects:	admixture population Biological and medical sciences Brazil - epidemiology Case-Control Studies Chromosomes, Human, Pair 8 Cleft Lip - epidemiology Cleft Lip - genetics cleft lip/palate common disease-common variant Facial bones, jaws, teeth, parodontium: diseases, semeiology Genetic Predisposition to Disease heritability Humans Interferon Regulatory Factors - genetics IRF6 transcription levels Linkage Disequilibrium Medical genetics Medical sciences mesenchymal stem cell Non tumoral diseases Otorhinolaryngology. Stomatology Polymorphism, Single Nucleotide Risk Factors rs590223 rs642961 structured association South America Brazil America common disease-common variant Cleft palate Cleft lip Transcription Pathogenesis Stem cell Mesenchyma cleft lip/palate Genetic determinism rs642961 Association Population Human IRF6 transcription levels mesenchymal stem cell Stomatology Congenital disease Variant structured association Malformation rs590223 Admixture Risk factor Oral cavity disease Heritability admixture population
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Summary:	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.
Bibliography:	istex:4C455A4E0E3046511C1932D0DCA78898A59409FF 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. CNPq, FAPESP and the Brazilian Ministry of Health ark:/67375/WNG-NGC20VG7-W ArticleID:AJMG35526 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. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1552-4825 1552-4833
DOI:	10.1002/ajmg.a.35526