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.
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.
Authors: Erika H Noss; Hung N Nguyen; Sook Kyung Chang; Gerald F M Watts; Michael B Brenner Journal: Proc Natl Acad Sci U S A Date: 2015-11-17 Impact factor: 11.205
Authors: Stacey E Alexeeff; Andrea A Baccarelli; Jaana Halonen; Brent A Coull; Robert O Wright; Letizia Tarantini; Valentina Bollati; David Sparrow; Pantel Vokonas; Joel Schwartz Journal: Int J Epidemiol Date: 2013-02 Impact factor: 7.196
Authors: Shaoping Zhang; Silvana P Barros; Antonio J Moretti; Ning Yu; Jing Zhou; John S Preisser; Mihai D Niculescu; Steven Offenbacher Journal: J Periodontol Date: 2013-01-31 Impact factor: 6.993