Studies with Wnt genes and nonsyndromic cleft lip and palate

Authors

  • Renato Menezes,

    1. Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    2. Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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    • R. Menezes and A. Letra contributed equally to this work.

  • Ariadne Letra,

    1. Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    2. Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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  • Ana H. Kim,

    1. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania
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  • Erika C. Küchler,

    1. Department of Cell and Molecular Biology, Fluminense Federal University, Rio de Janeiro, Brazil
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  • Alicia Day,

    1. Honors Biology Program, University of Michigan, Flint, Michigan
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  • Patricia N. Tannure,

    1. Department of Pediatric Dentistry and Orthodontics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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  • Luise Gomes da Motta,

    1. Restorative Dentistry and Dental Materials, Fluminense Federal University, Rio de Janeiro, Brazil
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  • Katiucia B.S. Paiva,

    1. Laboratory of Molecular Pathology, Department of Oral Pathology, Dental School, University of São Paulo, São Paulo, Brazil
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  • Jose M. Granjeiro,

    1. Department of Cell and Molecular Biology, Fluminense Federal University, Rio de Janeiro, Brazil
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  • Alexandre R. Vieira

    Corresponding author
    1. Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    2. Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    3. Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    4. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
    • Alexandre R. Vieira, 614 Salk Hall, Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15261
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  • 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.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

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