{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:34:15Z","timestamp":1786649655962,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"\n Background:<\/jats:title>\n \n Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. Conventional diagnostic markers for RA have limitations, prompting the exploration of DNA methylation analysis as a potential biomarker. This study focuses on evaluating the methylation levels of two genes,\n MMP9<\/jats:italic>\n and\n RUNX3<\/jats:italic>\n , in peripheral blood mononuclear cells (PBMCs) as potential biomarkers for RA.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n We assessed the methylation levels of the\n MMP9<\/jats:italic>\n and\n RUNX3<\/jats:italic>\n promoters in PBMCs from 72 RA patients and 72 healthy controls using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) method. The data were analyzed for diagnostic utility and correlation with clinical features, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n MMP9<\/jats:italic>\n methylation levels were significantly lower in RA patients compared to controls (38.23 \u00b1 28.62 vs. 62.27 \u00b1 19.68,\n P<\/jats:italic>\n < 0.001), indicating significant hypomethylation.\n RUNX3<\/jats:italic>\n methylation showed no significant difference between the groups (\n P<\/jats:italic>\n : 0.295). Receiver operating characteristic (ROC) curve analysis revealed a sensitivity of 73.61% and a specificity of 72.22% with an area under the ROC curve of 0.756 (\n P<\/jats:italic>\n < 0.001) for\n MMP9<\/jats:italic>\n .\n MMP9<\/jats:italic>\n methylation was negatively correlated with ESR and CRP levels (\n P<\/jats:italic>\n < 0.001), while\n RUNX3<\/jats:italic>\n showed positive correlations with ESR (\n P<\/jats:italic>\n : 0.014) and CRP (\n P<\/jats:italic>\n : 0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n The study suggests that\n MMP9<\/jats:italic>\n promoter hypomethylation may serve as a promising diagnostic and prognostic biomarker for RA. In addition,\n RUNX3<\/jats:italic>\n promoter methylation showed potential for assessing disease activity. These findings have the potential to improve the diagnosis and prognosis of RA, contributing to improved clinical management of patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/abr.abr_398_25","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T14:01:21Z","timestamp":1767103281000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Promoter Methylation of MMP9 and RUNX3: Diagnostic Potential and Clinical Associations in Rheumatoid Arthritis"],"prefix":"10.4103","volume":"14","author":[{"given":"Amir Mohamad","family":"Mohamadizad Moghadam","sequence":"first","affiliation":[{"name":"Student Research Committee, Aja University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran"},{"name":"Personalized Medicine and Genometabolomics Research Center, Hope Generation Foundation, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrouz","family":"Khoshbakht","sequence":"additional","affiliation":[{"name":"Genome Medical Genetics Lab, Arak, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhollah","family":"Mirjani","sequence":"additional","affiliation":[{"name":"Department of Genetics and Advanced Technologies, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Zarei","sequence":"additional","affiliation":[{"name":"Department of Genetics and Advanced Technologies, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Ghasemzadeh Soroush","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Aja University of Medical Sciences, Imam Reza Hospital, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyyed Mohamad","family":"Hoseini","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Semnan University of Medical Sciences, Semnan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meysam","family":"Mosallaei","sequence":"additional","affiliation":[{"name":"Personalized Medicine and Genometabolomics Research Center, Hope Generation Foundation, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,12]]},"reference":[{"key":"R1-20251230","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.3390\/cells10112857","article-title":"Management of rheumatoid arthritis: An 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