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Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA) and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (\n                    <jats:italic>MUC4<\/jats:italic>\n                    ) and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (\n                    <jats:italic>PLEK<\/jats:italic>\n                    ), was significantly overexpressed in periodontitis, CVD, RA and UC, implicating this gene as an important networking link between these chronic inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1038\/srep18475","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T05:05:33Z","timestamp":1450674333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases"],"prefix":"10.1038","volume":"5","author":[{"given":"Anna","family":"Lundmark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haleh","family":"Davanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tove","family":"B\u00e5ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Johannsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin","family":"Koro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joakim","family":"Lundeberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00fclay","family":"Yucel-Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,21]]},"reference":[{"key":"BFsrep18475_CR1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.tem.2015.03.001","volume":"26","author":"KE Kholy","year":"2015","unstructured":"Kholy, K. E., Genco, R. J. & Van Dyke, T. E. Oral infections and cardiovascular disease. Trends Endocrinol. Metab. 26, 315\u2013321 (2015).","journal-title":"Trends Endocrinol. Metab."},{"key":"BFsrep18475_CR2","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1177\/0022034512457373","volume":"91","author":"PI Eke","year":"2012","unstructured":"Eke, P. I. et al. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J. Dent. Res. 91, 914\u2013920 (2012).","journal-title":"J. Dent. Res."},{"key":"BFsrep18475_CR3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/nri3785","volume":"15","author":"G Hajishengallis","year":"2014","unstructured":"Hajishengallis, G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat. Rev. Immunol. 15, 30\u201344 (2014).","journal-title":"Nat. Rev. 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