Get access

Association of MMP3 and TIMP2 promoter polymorphisms with nonsyndromic oral clefts

Authors

  • Ariadne Letra,

    1. Department of Oral Biology and Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
    Current affiliation:
    1. Departments of Endodontics, School of Dentistry, and Pediatric Research Center, Medical School, University of Texas Health Science Center, Houston, Texas
    Search for more papers by this author
  • Renato M. Silva,

    1. Department of Oral Biology and Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
    Current affiliation:
    1. Departments of Endodontics, School of Dentistry, and Pediatric Research Center, Medical School, University of Texas Health Science Center, Houston, Texas
    Search for more papers by this author
  • Luise G. Motta,

    1. Department of Materials Science, School of Dentistry, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Susan H. Blanton,

    1. University of Miami Miller School of Medicine, Miami Florida
    Search for more papers by this author
  • Jacqueline T. Hecht,

    1. Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX
    Search for more papers by this author
  • Jose M. Granjeirol,

    1. Department of Cell and Molecular Biology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil
    Search for more papers by this author
  • Alexandre R. Vieira

    Corresponding author
    1. Department of Oral Biology and Center for Craniofacial and Dental Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
    • 614 Salk Hall, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15261
    Search for more papers by this author

  • Presented at the 12th International Congress of Human Genetics and 61st Annual Meeting of the American Society of Human Genetics, October 11–15, 2011, Montreal, Canada.

    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, National Center for Research Resources, or the National Institutes of Health.

Abstract

BACKGROUND Oral clefts are common congenital anomalies and result from defects during embryogenesis. The complex etiology is evident by the number of genes and signaling pathways involved in craniofacial development. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are responsible for tissue remodeling during craniofacial development. METHODS In this study, we investigated the association of polymorphisms in 14 biologically relevant MMP and TIMP genes in 494 individuals with oral clefts and 413 control individuals from Brazil. Genotypes were generated using Taqman chemistry. Analyses were performed using PLINK software. RESULTS Polymorphisms in MMP3 (rs522616) and TIMP2 (rs8179096) showed significant association with all cleft types (all clefts, cleft lip/palate, and cleft palate; p ≤ 0.002). An additional family-based dataset (881 case-parent trios) from the United States was used for confirmation of the association findings (p < 0.05). Analysis of gene-gene interaction suggests that MMP3 and TIMP2 may interactively contribute to a cleft phenotype. CONCLUSIONS This study provides new evidence that variation in MMP3 may contribute to nonsyndromic oral clefts and further supports the involvement of TIMP2 as a cleft susceptibility gene. Although additional studies are still necessary to unveil the exact mechanism by which MMP3 and TIMP2 would contribute to a cleft phenotype, allelic polymorphisms in these genes and their interactions may partly explain the variance of individual susceptibility to oral clefts. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.

Ancillary