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Association of MMP3 and TIMP2 promoter polymorphisms with nonsyndromic oral clefts

Letra, A and Silva, RM and Motta, LG and Blanton, SH and Hecht, JT and Granjeirol, JM and Vieira, AR (2012) Association of MMP3 and TIMP2 promoter polymorphisms with nonsyndromic oral clefts. Birth Defects Research Part A - Clinical and Molecular Teratology, 94 (7). 540 - 548. ISSN 1542-0752

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Letra, A
Silva, RM
Motta, LG
Blanton, SH
Hecht, JT
Granjeirol, JM
Vieira, ARarv11@pitt.eduARV11
Date: 1 July 2012
Date Type: Publication
Journal or Publication Title: Birth Defects Research Part A - Clinical and Molecular Teratology
Volume: 94
Number: 7
Page Range: 540 - 548
DOI or Unique Handle: 10.1002/bdra.23026
Schools and Programs: School of Dental Medicine > Dental Science
Refereed: Yes
ISSN: 1542-0752
Other ID: NLM NIHMS373427, NLM PMC3393800
PubMed Central ID: PMC3393800
PubMed ID: 22730240
Date Deposited: 24 Sep 2012 19:08
Last Modified: 20 Feb 2020 13:55


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