{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:21:11Z","timestamp":1791181271456,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22592309"],"award-info":[{"award-number":["22592309"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> 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\u20106 (IL\u20106) gene promoter was unique to individuals with RA and CP.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The study participants consisted of 30 patients with RA, 30 patients with CP, and 30 age\u2010, sex\u2010, and smoking status\u2013balanced healthy controls. Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed for DNA methylation levels of IL\u20106 gene with direct sequencing. Levels of IL\u20106 were determined by an enzyme\u2010linked immunosorbent assay.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The region of IL\u20106 gene promoter from \u22121200 to +27 bp was shown to contain 19 CpG motifs. The methylation levels of the CpG motif at \u221274 bp were significantly lower in patients with RA and CP than those in controls (<jats:italic>P<\/jats:italic> = 0.0001). Both levels of serum IL\u20106 and IL\u20106 production by mononuclear cells were significantly different between individuals with and without the methylation at \u221274 bp (<jats:italic>P<\/jats:italic> = 0.03). The +19 bp motif exhibited differential levels of the methylation among the groups, which was not associated with serum levels of IL\u20106. The other 17 CpG motifs exhibited comparable levels of the methylation between the groups.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> These results suggest that hypomethylated status of a single CpG in the IL\u20106 promoter region may lead to increased levels of serum IL\u20106, implicating a role in the pathogenesis of RA and CP.<\/jats:p>","DOI":"10.1902\/jop.2011.110356","type":"journal-article","created":{"date-parts":[[2011,11,28]],"date-time":"2011-11-28T10:02:28Z","timestamp":1322474548000},"page":"917-925","source":"Crossref","is-referenced-by-count":113,"title":["Interleukin\u20106 Gene Promoter Methylation in Rheumatoid Arthritis and Chronic Periodontitis"],"prefix":"10.1002","volume":"83","author":[{"given":"Kohei","family":"Ishida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moe","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asami","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Murasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Yoshie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1650","article-title":"Adult 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