Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 29 1 2026 01 01 Hypomethylation of the Human OAS2 Gene in Blood Cells as a Potential Biomarker for Rheumatoid Arthritis: Findings from an Iranian Case-control Study 12 20 10.34172/aim.35446 EN Delnya Gholami https://orcid.org/0000-0003-4762-0859 Zahra Ourang Mohammad Saatchi Esmat Rigi Yousefabadi Emran Esmaeilzadeh Masoumeh Akhlaghi Hoda Kavosi Hamid Reza Khorram Khorshid https://orcid.org/0000-0003-0357-1573 Journal Article 10.34172/aim.35446 2025 11 17 2025 12 14 Background: Given the pivotal role of DNA methylation in the progression and severity of rheumatoid arthritis (RA), identifying a unique methylation pattern associated with the disease could support early detection, disease monitoring, and the development of personalized treatment plans. We aimed to explore the potential of OAS2 and OAS3 methylation levels in peripheral blood cells. These levels could be used to diagnose RA and predict patient outcomes. Methods: We collected 105 peripheral blood specimens from RA patients and 110 from healthy subjects. We then performed methylation analysis using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) technique. Finally, we analyzed the data using appropriate nonparametric tests. Results: Our study revealed a significant decrease in OAS2 gene methylation in RA patients (P<0.001). The ROC curve analysis further underscored the potential of OAS2 DNA methylation (AUC=0.718, P<0.001) to effectively distinguish RA patients from healthy individuals. Although OAS2 methylation was generally reduced in RA patients compared to controls, RA patients with a positive family history exhibited higher methylation than those without (P=0.018). Moreover, increased OAS2 methylation was associated with reduced CRP levels (r=-0.317, P<0.001). Conclusion: The methylation levels of OAS2 in peripheral blood cells show promise in distinguishing RA patients from healthy individuals. Furthermore, these levels show potential in identifying inflammation, a family history of RA, and other related disorders.