title: Interleukin-6 gene promoter methylation in rheumatoid arthritis and chronic periodontitis.
abstract: BACKGROUND
  Methylation status of the cytokine genes may play a role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA) and chronic periodontitis (CP). This study was undertaken to evaluate whether the DNA methylation profile of the interleukin-6 (IL-6) gene promoter was unique to individuals with RA and CP.
  
  
  METHODS
  The study participants consisted of 30 patients with RA, 30 patients with CP, and 30 age-, sex-, and smoking status-balanced healthy controls. Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed for DNA methylation levels of IL-6 gene with direct sequencing. Levels of IL-6 were determined by an enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The region of IL-6 gene promoter from -1200 to +27 bp was shown to contain 19 CpG motifs. The methylation levels of the CpG motif at -74 bp were significantly lower in patients with RA and CP than those in controls (P = 0.0001). Both levels of serum IL-6 and IL-6 production by mononuclear cells were significantly different between individuals with and without the methylation at -74 bp (P = 0.03). The +19 bp motif exhibited differential levels of the methylation among the groups, which was not associated with serum levels of IL-6. The other 17 CpG motifs exhibited comparable levels of the methylation between the groups.
  
  
  CONCLUSIONS
  These results suggest that hypomethylated status of a single CpG in the IL-6 promoter region may lead to increased levels of serum IL-6, implicating a role in the pathogenesis of RA and CP.
authors: Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors: Kohei
authors: K
authors: Ishida
authors: Tetsuo
authors: T
authors: Kobayashi
authors: Satoshi
authors: S
authors: Ito
authors: Yasutaka
authors: Y
authors: Komatsu
authors: Tomoko
authors: T
authors: Yokoyama
authors: Moe
authors: M
authors: Okada
authors: Asami
authors: A
authors: Abe
authors: Akira
authors: A
authors: Murasawa
authors: Hiromasa
authors: H
authors: Yoshie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D020029:Base Pairing / Q000235:genetics; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000145:classification / Q000235:genetics / Q000276:immunology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; 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*; D017422:Sequence Analysis, DNA; D012907:Smoking
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides