title: Analysis of multiple cytokine polymorphisms in individuals with untreated deep carious lesions reveals IL1B (rs1143643) as a susceptibility factor for periapical lesion development.
abstract: BACKGROUND
  It has been proposed that individual genetic predisposition may contribute to persistent apical periodontitis. Cytokines are associated with levels of inflammation and are involved in caries, pulpal, and periapical tissue destruction. We hypothesized that polymorphisms in cytokine genes may contribute to an individual's increased susceptibility to apical tissue destruction in response to deep carious lesions.
  
  
  METHODS
  Subjects with deep carious lesions with or without periapical lesions (≥3 mm) were recruited at the University of Pittsburgh, Pittsburgh, PA, and the University of Texas at Houston, Houston, TX. Genomic DNA samples of 316 patients were sorted into 2 groups: 136 cases with deep carious lesions and periapical lesions (cases) and 180 cases with deep carious lesions but no periapical lesions (controls). Nine single-nucleotide polymorphisms in IL1B, IL6, TNF, RANK, RANKL, and OPG genes were selected for genotyping. Genotypes were generated by end point analysis using TaqMan chemistry (Invitrogen, Carlsbad, CA) in a real-time polymerase chain reaction instrument. Allele and genotype frequencies were compared among cases and controls using the PLINK program (http://pngu.mgh.harvard.edu/purcell/plink/). Ninety-three human periapical granulomas and 24 healthy periodontal ligament tissues collected postoperatively were used for messenger RNA expression analyses of IL1B.
  
  
  RESULTS
  A single-nucleotide polymorphism in IL1B (rs1143643) showed allelic (P = .02) and genotypic (P = .004) association with cases of deep caries and periapical lesions. We also observed altered transmission of IL1B marker haplotypes (P = .02) in these individuals. IL1B was highly expressed in granulomas (P < .001).
  
  
  CONCLUSIONS
  Variations in IL1B may be 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.
authors.forename: Alisa
authors.initials: A
authors.lastname: Dill
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Letícia
authors.initials: L
authors.lastname: Chaves de Souza
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Mamatha
authors.initials: M
authors.lastname: Yadlapati
authors.affiliation: Osteoimmunology Lab, Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Brazil.
authors.forename: Claudia Cristina
authors.initials: CC
authors.lastname: Biguetti
authors.affiliation: Osteoimmunology Lab, Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Brazil.
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas. Electronic address: Renato.M.Silva@uth.tmc.edu.
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D003731:Dental Caries / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010482:Periapical Abscess / Q000235:genetics / Q000503:physiopathology; D010485:Periapical Periodontitis / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D019227:Tooth Apex / Q000503:physiopathology
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta
keywords: Apical periodontitis; cytokines; genetic polymorphisms