title: Polymorphisms in genes involved in enamel development are associated with dental fluorosis.
abstract: OBJECTIVE
  To evaluate the association between polymorphisms in DLX1, DLX2, MMP13, TIMP1 and TIMP2 genes with dental fluorosis (DF) phenotype.
  
  
  METHODS
  Four hundred and eighty one subjects (108 with DF and 373 DF free) from 6 to 18 years of age were recruited. This population lived in Rio de Janeiro, a city with fluoridation of public water supplies. DF was assessed using the Deańs index modified. Only erupted permanent teeth were assessed. Genetic polymorphisms in DLX1, DLX2, MMP13, TIMP1 and TIMP2 were analyzed by real-time PCR from genomic DNA. Association between DF, genotype, and allele distribution were evaluated using chi-square and logistic regression analyses with an alpha level of 5%.
  
  
  RESULTS
  DF was more prevalent in Afro-descendants than in Caucasians (p=0.08; OR=1.83; CI 95%=1.18-2.82). Logistic regression analysis adjusted by the ethnicity demonstrated a statistical difference for TIMP1 genotype (p=0.033; OR=2.93, 95%CI, 1.09-7.90). When only the severer cases of DF were analyzed, polymorphisms in DLX1 and DLX2 were associated with DF (p<0.05).
  
  
  CONCLUSIONS
  Our results provided evidence that polymorphisms in TIMP1, DLX1 and DLX2 genes may be associated with DF phenotypes.
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: erikacalvano@gmail.com.
authors.forename: Erika Calvano
authors.initials: EC
authors.lastname: Küchler
authors.affiliation: School of Dentistry, Veiga de Almeida University, Rio de Janeiro-RJ, Brazil; Postgraduate Program in Dentistry, Fluminense Federal University, Niterói, Brazil. Electronic address: pntannure@gmail.com.
authors.forename: Patricia Nivoloni
authors.initials: PN
authors.lastname: Tannure
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: barrosodaniela@hotmail.com.
authors.forename: Daniela Silva Barroso de
authors.initials: DS
authors.lastname: Oliveira
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil. Electronic address: sendacharone@yahoo.com.br.
authors.forename: Senda
authors.initials: S
authors.lastname: Charone
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: nelson@forp.usp.br.
authors.forename: Paulo
authors.initials: P
authors.lastname: Nelson-Filho
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Raquel Assed Bezerra da
authors.initials: RA
authors.lastname: Silva
authors.affiliation: Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Rio de Janeiro-RJ, Brazil. Electronic address: pttpo2009@yahoo.com.br.
authors.forename: Marcelo de Castro
authors.initials: MC
authors.lastname: Costa
authors.affiliation: Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil; Postgraduate Program in Dentistry, Fluminense Federal University, Niterói, Brazil. Electronic address: leonardoantunes@id.uff.br.
authors.forename: Leonardo Santos
authors.initials: LS
authors.lastname: Antunes
authors.affiliation: Postgraduate Program in Dentistry, Fluminense Federal University, Niterói, Brazil. Electronic address: monicacalasansmaia@gmail.com.
authors.forename: Mônica Diuana
authors.initials: MD
authors.lastname: Calasans Maia
authors.affiliation: Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil; Postgraduate Program in Dentistry, Fluminense Federal University, Niterói, Brazil. Electronic address: liviaazeredo@gmail.com.
authors.forename: Lívia Azeredo Alves
authors.initials: LA
authors.lastname: Antunes
mesh_terms: D000293:Adolescent; D000483:Alleles; D000566:Amelogenesis / Q000235:genetics*; D001938:Brazil; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D009050:Fluorosis, Dental / Q000235:genetics*; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C000619438:DLX2 protein, human; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D019716:Tissue Inhibitor of Metalloproteinase-2; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Dental fluorosis; Gene; Polymorphism