{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:51:28Z","timestamp":1790794288525,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Transl Gastroenterol","Clinical and Translational Gastroenterology"],"abstract":"<jats:sec>\n                    <jats:title>INTRODUCTION:<\/jats:title>\n                    <jats:p>DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We included 103 participants and grouped them into 2 cohorts (a first [n = 31] and a second validation [n = 72] cohort), with active CD (aCD) and inactive CD (iCD) and healthy participants (CTR). DNA was obtained from the peripheral blood and analyzed by the Agena platform. The selected genes were catalase (\n                      <jats:italic toggle=\"yes\">CAT<\/jats:italic>\n                      ), \u03b1-defensin 5 (\n                      <jats:italic toggle=\"yes\">DEFA5<\/jats:italic>\n                      ),\n                      <jats:italic toggle=\"yes\">FasR, FasL,<\/jats:italic>\n                      tumor necrosis factor (\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      ),\n                      <jats:italic toggle=\"yes\">TNFRSF1A, TNFRSF1B,<\/jats:italic>\n                      <jats:italic toggle=\"yes\">PPA2, ABCB1, NOD2, PPAR\u03b3,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PKC\u03b6<\/jats:italic>\n                      . We used the elastic net algorithm and R software.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We studied 240 CpGs. Sixteen CpGs showed differential methylation profiles among aCD, iCD, and CTR. We selected for validation those with the greatest differences:\n                      <jats:italic toggle=\"yes\">DEFA5<\/jats:italic>\n                      CpG_11; CpG_13;\n                      <jats:italic toggle=\"yes\">CAT<\/jats:italic>\n                      CpG_31.32;\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      CpG_4, CpG_12; and\n                      <jats:italic toggle=\"yes\">ABCB1<\/jats:italic>\n                      CpG_21. Our results validated the genes\n                      <jats:italic toggle=\"yes\">DEFA5<\/jats:italic>\n                      (methylation gain) and\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      (methylation loss) with\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      values &lt; 0.001. In both cases, the methylation level was maintained and did not change with CD activity (aCD vs iCD). The subanalysis comparison between aCD and iCD showed significant differential methylation profiles in other CpGs:\n                      <jats:italic toggle=\"yes\">TNF, FAS,<\/jats:italic>\n                      <jats:italic toggle=\"yes\">ABCB1, CAT,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TNFRS1BF<\/jats:italic>\n                      genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION:<\/jats:title>\n                    <jats:p>\n                      The methylation status of\n                      <jats:italic toggle=\"yes\">DEFA5<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      genes provides a signature biomarker that characterizes patients with CD and supports the possible implication of the environment and the immune system in CD pathogenesis.\n   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Digestive Diseases Network (Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas[CIBEREHD]), Madrid, Spain;"},{"name":"Department of Gastroenterology, Hospital La Fe, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Biomarkers and Precision Medicine Unit, Health Research Institute La Fe (IIS La Fe), Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Bus\u00f3","sequence":"additional","affiliation":[{"name":"Central Unit for Research in Medicine (UCIM),University of Valencia, Valencia, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Tortosa","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), Valencia, Spain;"},{"name":"Biomedical Research Centre, Hepatic and Digestive 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