{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:23:24Z","timestamp":1769761404801,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T00:00:00Z","timestamp":1438819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"the Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["25253104"],"award-info":[{"award-number":["25253104"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Over\u2010expression of tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) 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\u2010\u03b1 gene promoter in blood cells of individuals with CP and RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>The study participants consisted of 30 Japanese adults with RA (RA group), 30 race\u2010matched adults with CP only (CP group) and 30 race\u2010matched 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\u2010\u03b1 gene promoter region. The level of TNF\u2010\u03b1 produced in mononuclear cells stimulated with <jats:italic>Porphyromonas gingivalis<\/jats:italic> lipopolysaccharide was determined using ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve cytosine\u2013guanine dinucleotide (CpG) motifs were identified in the TNF\u2010\u03b1 promoter fragment from \u2212343 to +57\u00a0bp. The CP group showed a significantly higher methylation rate and frequency at \u221272\u00a0bp than the H group (<jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.01). The RA group exhibited significantly higher methylation rates at seven CpG motifs (\u2212302, \u2212163, \u2212119, \u221272, \u221249, \u221238 and +10\u00a0bp), and significantly higher methylation frequencies at six CpG motifs (\u2212163, \u2212119, \u221272, \u221249, \u221238 and +10\u00a0bp), than the H group (<jats:italic>p\u00a0<\/jats:italic>&lt;<jats:italic>\u00a0<\/jats:italic>0.01 for all comparisons). The levels of TNF\u2010\u03b1 produced were significantly different between individuals with and without methylation at \u2212163\u00a0bp (<jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that the hypermethylated status of CpG motifs in the TNF\u2010\u03b1 gene promoter in blood cells may be unique to Japanese adults with CP and RA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12314","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T13:52:58Z","timestamp":1438869178000},"page":"350-358","source":"Crossref","is-referenced-by-count":39,"title":["Tumor necrosis factor\u2010alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis"],"prefix":"10.1111","volume":"51","author":[{"given":"A.","family":"Kojima","sequence":"first","affiliation":[{"name":"Division of Periodontology Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Periodontology Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"General Dentistry and Clinical Education Unit Niigata University Medical and Dental Hospital Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Ito","sequence":"additional","affiliation":[{"name":"Niigata Rheumatic Center Shibata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Murasawa","sequence":"additional","affiliation":[{"name":"Niigata Rheumatic Center Shibata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Nakazono","sequence":"additional","affiliation":[{"name":"Niigata Rheumatic Center Shibata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Yoshie","sequence":"additional","affiliation":[{"name":"Division of Periodontology Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata 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