R. Menezes and A. Letra contributed equally to this work.
Studies with Wnt genes and nonsyndromic cleft lip and palate†
Article first published online: 1 OCT 2010
Copyright © 2010 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 88, Issue 11, pages 995–1000, November 2010
How to Cite
Menezes, R., Letra, A., Kim, A. H., Küchler, E. C., Day, A., Tannure, P. N., da Motta, L. G., Paiva, K. B.S., Granjeiro, J. M. and Vieira, A. R. (2010), Studies with Wnt genes and nonsyndromic cleft lip and palate. Birth Defects Research Part A: Clinical and Molecular Teratology, 88: 995–1000. doi: 10.1002/bdra.20720
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Dental and Craniofacial Research or the National Institutes of Health.
- Issue published online: 23 NOV 2010
- Article first published online: 1 OCT 2010
- Manuscript Accepted: 8 JUL 2010
- Manuscript Revised: 6 JUL 2010
- Manuscript Received: 15 MAY 2010
- Carnegie Mellon Undergraduate Research Office (URO)
- NIH. Grant Numbers: 1K99DE018413-01A1, 1K99DE018954, UL1 RR024153
- Wnt pathway;
- cleft lip/palate;
- tooth agenesis;
Clefts of the lip and/or palate (cleft lip/palate) are notable for their complex etiology. The WNT pathway regulates multiple developmental processes including craniofacial development and may play a role in cleft lip/palate and other defects of craniofacial development such as tooth agenesis. Variations in WNT genes have been recently associated with cleft lip/palate in humans. In addition, two WNT genes, Wnt3 and Wnt9B, are located in the clf1 cleft locus in mice.
We investigated 13 SNPs located in Wnt3A, Wnt5A, Wnt8A, Wnt11, Wnt3, and Wnt9B genes for association with cleft lip/palate subphenotypes in 463 cleft cases and 303 unrelated controls. Genotyping of selected polymorphisms was carried out using Taqman assays. PLINK 1.06 software was used to test for differences in allele frequencies of each polymorphism between affected and unaffected individuals. Haplotype analysis was also performed.
Individuals carrying variant alleles in WNT3 presented an increased risk for cleft lip/palate (p = 0.0003; OR, 1.61; 95% CI, 1.29–2.02) in the population studied.
Our results continue to support a role for WNT genes in the pathogenesis of cleft lip/palate. Although much remains to be learned about the function of individual WNT genes during craniofacial development, additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.