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Interleukin‐6 Gene Promoter Methylation in Rheumatoid Arthritis and Chronic Periodontitis
Author(s) -
Ishida Kohei,
Kobayashi Tetsuo,
Ito Satoshi,
Komatsu Yasutaka,
Yokoyama Tomoko,
Okada Moe,
Abe Asami,
Murasawa Akira,
Yoshie Hiromasa
Publication year - 2012
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2011.110356
Subject(s) - methylation , dna methylation , cpg site , promoter , bisulfite sequencing , gene , microbiology and biotechnology , rheumatoid arthritis , pathogenesis , biology , immunology , gene expression , genetics
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. Conclusion: 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.