title: Heat Shock 70 Protein Genes and Genetic Susceptibility to Apical Periodontitis.
abstract: BACKGROUND
  Heat shock proteins (HSPs) protect cells under adverse conditions such as infection, inflammation, and disease. The differential expression of HSPs in human periapical granulomas suggests a potential role for these proteins in periapical lesion development, which may contribute to different clinical outcomes. Therefore, we hypothesized that polymorphisms in HSP genes leading to perturbed gene expression and protein function may contribute to an individual's susceptibility to periapical lesion development.
  
  
  METHODS
  Subjects with deep carious lesions with or without periapical lesions (≥3 mm) were recruited at the University of Texas School of Dentistry at Houston and at the University of Pittsburgh. Genomic DNA samples of 400 patients were sorted into 2 groups: 183 cases with deep carious lesions and periapical lesions (cases) and 217 cases with deep carious lesions but without periapical lesions (controls). Eight single nucleotide polymorphisms (SNPs) in HSPA4, HSPA6, HSPA1L, HSPA4L, and HSPA9 genes were selected for genotyping. Genotypes were generated by end point analysis by using Taqman chemistry in a real-time polymerase chain reaction assay. Allele and genotype frequencies were compared among cases and controls by using χ(2) and Fisher exact tests as implemented in PLINK v.1.07. In silico analysis of SNP function was performed by using Polymorphism Phenotyping V2 and MirSNP software.
  
  
  RESULTS
  Overall, SNPs in HSPA1L and HSPA6 showed significant allelic association with cases of deep caries and periapical lesions (P < .05). We also observed altered transmission of HSPA1L SNP haplotypes (P = .03). In silico analysis of HSPA1L rs2075800 function showed that this SNP results in a glutamine-to-lysine substitution at position 602 of the protein and might affect the stability and function of the final protein.
  
  
  CONCLUSIONS
  Variations in HSPA1L and HSPA6 may be associated with periapical lesion formation in individuals with untreated deep carious lesions. Future studies could help predict host susceptibility to developing apical periodontitis.
authors: Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors: Kanwal
authors: K
authors: Maheshwari
authors: Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas; Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors: Renato M
authors: RM
authors: Silva
authors: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors: Leticia
authors: L
authors: Guajardo-Morales
authors: Department of Biological Sciences, Bauru School of Dentistry, University of Sao Paulo, Bauru, São Paulo, Brazil.
authors: Gustavo P
authors: GP
authors: Garlet
authors: Department of Oral Biology, Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pediatric Dentistry, Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Alexandre R
authors: AR
authors: Vieira
authors: Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas; Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas. Electronic address: Ariadne.M.Letra@uth.tmc.edu.
authors: Ariadne
authors: A
authors: Letra
mesh_terms: D004247:DNA / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D010485:Periapical Periodontitis / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D018840:HSP70 Heat-Shock Proteins; D004247:DNA
keywords: Apical periodontitis; heat shock proteins; polymorphism