title: Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis.
abstract: OBJECTIVE
  Over-expression of tumor necrosis factor-alpha (TNF-α) plays a pathological role in chronic periodontitis (CP) and rheumatoid arthritis (RA), which might be regulated by the epigenetic mechanism. The aim of the present study was to evaluate whether there is a unique methylation profile of the TNF-α gene promoter in blood cells of individuals with CP and RA.
  
  
  METHODS
  The study participants consisted of 30 Japanese adults with RA (RA group), 30 race-matched adults with CP only (CP group) and 30 race-matched healthy controls (H group). Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed, by direct sequencing, to investigate DNA methylation of the TNF-α gene promoter region. The level of TNF-α produced in mononuclear cells stimulated with Porphyromonas gingivalis lipopolysaccharide was determined using ELISA.
  
  
  RESULTS
  Twelve cytosine-guanine dinucleotide (CpG) motifs were identified in the TNF-α promoter fragment from -343 to +57 bp. The CP group showed a significantly higher methylation rate and frequency at -72 bp than the H group (p < 0.01). The RA group exhibited significantly higher methylation rates at seven CpG motifs (-302, -163, -119, -72, -49, -38 and +10 bp), and significantly higher methylation frequencies at six CpG motifs (-163, -119, -72, -49, -38 and +10 bp), than the H group (p < 0.01 for all comparisons). The levels of TNF-α produced were significantly different between individuals with and without methylation at -163 bp (p = 0.03).
  
  
  CONCLUSIONS
  These results suggest that the hypermethylated status of CpG motifs in the TNF-α gene promoter in blood cells may be unique to Japanese adults with CP and RA.
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kojima
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|General Dentistry and Clinical Education Unit, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Niigata Rheumatic Center, Shibata, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.affiliation: Niigata Rheumatic Center, Shibata, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Murasawa
authors.affiliation: Niigata Rheumatic Center, Shibata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakazono
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D055113:Chronic Periodontitis / Q000235:genetics / Q000276:immunology*; D019175:DNA Methylation / Q000235:genetics*; D015226:Dinucleoside Phosphates / Q000302:isolation & purification; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D059372:Nucleotide Motifs / Q000235:genetics; D017622:Periodontal Attachment Loss / Q000145:classification; D010514:Periodontal Pocket / Q000145:classification; D016966:Porphyromonas gingivalis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D015226:Dinucleoside Phosphates; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C015772:CpG dinucleotide
keywords: DNA methylation; periodontitis; rheumatoid arthritis; tumor necrosis factor-alpha