title: MMP1-1607 polymorphism increases the risk for periapical lesion development through the upregulation MMP-1 expression in association with pro-inflammatory milieu elements.
abstract: OBJECTIVE
  In this study, we evaluated the association between the MMP1-1607 polymorphism (rs1799750) and pro-inflammatory milieu elements with MMP-1 mRNA levels in vivo.
  
  
  METHODS
  MMP1-1607 SNP and the mRNA levels of MMP-1, TNF-a, IFN-g, IL-17A, IL-21, IL-10, IL-4, IL-9, and FOXp3 were determined via RealTimePCR in DNA/RNA samples from patients presenting periapical granulomas (N=111, for both genotyping and expression analysis) and control subjects (N=214 for genotyping and N=26 for expression analysis). The Shapiro-Wilk, Fisher, Pearson, Chi-square ordinal least squares regression tests were used for data analysis (p<0.05 was considered statistically significant).
  
  
  RESULTS
  The MMP1-1607 1G/2G and 1G/2G+2G/2G genotypes were significantly more prevalent in the patients than in controls, comprising a risk factor for periapical lesions development. MMP-1 mRNA levels were higher in periapical lesions than in healthy periodontal ligament samples, as well as higher in active than in inactive lesions. The polymorphic allele 2G carriers presented a significantly higher MMP-1 mRNA expression when compared with the 1G/1G genotype group. The ordered logistic regression demonstrated a significant correlation between the genetic polymorphism and the expression levels of MMP-1. Additionally, the pro- and anti-inflammatory cytokines IL-17A, IFN-g, TNF-a, IL-21, IL-10, IL-9, and IL-4 were significant as complementary explanatory variables of MMP-1 expression.
  
  
  CONCLUSIONS
  The MMP1-1607 SNP was identified as a risk factor for periapical lesions development, possibly due to its association with increased MMP-1 mRNA levels in periapical lesions. The MMP-1 expression is also under the control of the inflammatory milieu elements, being the cytokines TNF-a, IL-21, IL-17A, and IFN-g associated with increased MMP-1 levels in periapical lesions, while IL-10, IL-9, or IL-4 presented an inverse association.
authors.affiliation: - Universidade do Sagrado Coração, Departamento de Ciências Biológicas e da Saúde, Bauru, SP, Brasil.
authors.forename: Ana Paula Favaro
authors.initials: AP
authors.lastname: Trombone
authors.affiliation: - Universidade de São Paulo, Faculdade de Odontologia de Bauru, Departamento de Ciências Biológicas, Bauru, SP, Brasil.|- Universidad de Chile, Facultad de Odontología, Departamento de Odontología Conservadora, Santiago, Chile.
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalla
authors.affiliation: - Universidade do Sagrado Coração, Departamento de Ciências Biológicas e da Saúde, Bauru, SP, Brasil.
authors.forename: Elcia Maria Varize
authors.initials: EM
authors.lastname: Silveira
authors.affiliation: - Universidade do Sagrado Coração, Departamento de Ciências Biológicas e da Saúde, Bauru, SP, Brasil.
authors.forename: Camile Bermejo
authors.initials: CB
authors.lastname: Andreo
authors.affiliation: - Universidade de São Paulo, Faculdade de Odontologia de Bauru, Departamento de Ciências Biológicas, Bauru, SP, Brasil.
authors.forename: Carolina Favaro
authors.initials: CF
authors.lastname: Francisconi
authors.affiliation: - Universidade de São Paulo, Faculdade de Odontologia de Bauru, Departamento de Ciências Biológicas, Bauru, SP, Brasil.
authors.forename: Angélica Cristina
authors.initials: AC
authors.lastname: Fonseca
authors.affiliation: - University of Texas Health Science Center at Houston, School of Dentistry, Department of Endodontics, Houston, USA.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.affiliation: - University of Texas Health Science Center at Houston, School of Dentistry, Department of Endodontics, Houston, USA.
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
authors.affiliation: - Universidade de São Paulo, Faculdade de Odontologia de Bauru, Departamento de Ciências Biológicas, Bauru, SP, Brasil.
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis* / Q000235:genetics*; D008875:Middle Aged; D010483:Periapical Diseases / Q000235:genetics*; D010484:Periapical Granuloma / Q000235:genetics; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D016207:Cytokines; D005819:Genetic Markers; D020781:Matrix Metalloproteinase 1