Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 8 2 2025 03 04 248 255 Golshid Sanati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mehrdad Noruzinia Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Naser Ebrahimi Daryani Department of Internal Medicine, Division of Gastroenterology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran Davood Jafari Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mohammad Ahmadvand Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Shahram Teimourian Department of Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Nima Rezaei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5 Research Center for Immunodeficiencies, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA 2025 03 04 2025 03 04 Background: Growing evidence supports that changes in the expression of the suppressor of cytokine signaling 3 (SOCS3) protein contribute to the pathogenesis of types of inflammatory bowel diseases (IBDs), including ulcerative colitis (UC). Despite the importance of the currently known genetic risk map, an increasing number of observations reveal that epigenetic modifications, including DNA methylation, are considered as or even more important for IBD pathogenesis than genetic predisposition. We investigated the hypothesis that alterations in DNA methylation status at the promoter region within the SOCS3 gene in colorectal tissue specimens may be involved in the susceptibility to UC. Methods: We studied extracted DNA from colorectal biopsies of 15 ulcerative colitis cases and 15 age—and sex-matched healthy controls and performed genotype analyses of the promoter methylation status of the SOCS3 gene, using the real-time quantitative multiplex methylation-specific PCR (QM-MSP) assay to show evidence of differential methylation between cases of ulcerative colitis and healthy controls. Results: Based on methylation assay data profiling, we found that the mean CpG island methylation levels at the SOCS3 gene promoter region in colorectal mucosa of patients with UC was significantly higher than mucosa from healthy controls (ulcerative colitis vs. healthy controls; 0.00007±0.0018 vs. 0.07±0.142, p<0.000). Conclusion: Our data provide an important insight into the influence of epigenetic aberrances in the SOCS3 gene such that the inactivation of the SOCS3 gene by promoter hypermethylation might be a risk factor for inflamed mucosa of UC. It might also fundamentally contribute to the initiation of the inflammatory process and development of UC. https://igj.tums.ac.ir/index.php/igj/article/view/203 https://igj.tums.ac.ir/index.php/igj/article/download/203/181