title: Genetic susceptibility to periapical disease: conditional contribution of MMP2 and MMP3 genes to the development of periapical lesions and healing response.
abstract: BACKGROUND
  It has been proposed that individual genetic predisposition may contribute to a persistent apical periodontitis condition. Matrix metalloproteinases (MMPs) are associated with levels of inflammation and are involved in caries, pulpal, and periapical tissue destruction. MMPs also play a major role in bone resorption. In this study, we hypothesized that polymorphisms in MMP genes and their regulators may contribute to an individual's increased susceptibility to apical tissue destruction in response to deep carious lesions.
  
  
  METHODS
  Sixteen hundred radiographic records obtained through the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository were screened for subjects with deep carious lesions in dentin with or without periapical lesions (≥ 3 mm). DNA samples of 268 patients were sorted into 2 groups: 158 cases with deep carious lesions but no periapical lesions (controls) and 110 cases with periapical lesions and deep carious lesions (cases). Sixteen SNP markers in MMP2, MMP3, MMP9, MMP13, MMP14, and TIMP2, were selected for genotyping. Genotypes were generated by endpoint analysis in a real-time polymerase chain reaction instrument. Analyses were performed comparing cases and controls. Allele and genotypic frequencies and haplotype analysis were calculated using the PLINK program.
  
  
  RESULTS
  An association was found for MMP3 rs639752 (P = .03) and rs679620 (P = .004) genotypes in individuals with periapical lesions. We also observed altered transmission of MMP2 marker haplotypes (P = .000004) in these individuals.
  
  
  CONCLUSIONS
  Variations in MMP2 and MMP3 are associated with periapical lesion formation in individuals with untreated deep carious lesions. Future studies could help predict host susceptibility to developing periapical lesions.
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Renato
authors.initials: R
authors.lastname: Menezes-Silva
authors.forename: Shahryar
authors.initials: S
authors.lastname: Khaliq
authors.forename: Kathleen
authors.initials: K
authors.lastname: Deeley
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
mesh_terms: D000225:Adenine; D003731:Dental Caries / Q000201:enzymology; D003790:Dental Pulp Necrosis / Q000235:genetics; D003804:Dentin / Q000201:enzymology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D010485:Periapical Periodontitis / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011480:Protease Inhibitors / Q000032:analysis; D013941:Thymine; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
chemical_list: D011480:Protease Inhibitors; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D006147:Guanine; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D000225:Adenine; D013941:Thymine