Association of Aberrant Promoter Methylation Changes in the Suppressor of Cytokine  Signaling 3 (SOCS3) Gene with Susceptibility to Crohn's Disease

Golshid  Sanati; Davood  Jafari; Mehrdad  Noruzinia; Naser  Ebrahimi Daryani; Mohammad  Ahmadvand; Shahram  Teimourian; Nima  Rezaei

doi:10.18502/ajmb.v14i2.8887

Golshid Sanati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Davood Jafari Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, 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
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

DOI: https://doi.org/10.18502/ajmb.v14i2.8887

Keywords: Crohn's disease, DNA methylation, Epigenetics, Immune regulation, SOCS3

Abstract

Background: Growing evidence supports that changes in the methylation state of Inflammatory Bowel Disease (IBD)-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We supposed that alterations in DNA methylation status at promoter region within the suppressor of cytokine signaling 3 (SOCS3) gene in intestinal tissues may be involved in the susceptibility to Crohn's Disease (CD).

Methods: DNA methylation status in the promoter region of the human SOCS3 gene of intestinal tissues from 15 patients with CD and 15 age- and sex-matched healthy controls were profiled using the real-time Quantitative Multiplex Methylation Specific PCR (QM-MSP) assay.

Results: Based on methylation assay data profiling, we found that patients with CD showed a higher degree of methylation of the SOCS3 gene promoter region than did the healthy controls (unmethylated DNA in CD vs. healthy controls; 0.00048±0.0011 vs. 0.07±0.142, p<0.000).

Conclusion: The data presented here demonstrate that aberrant methylation of the CpG islands within promoter regions of SOCS3 gene in colonic mucosa of CD was associated with mucosal inflammatory status, providing insights into the involvement of methylation could contribute to the initiation of the inflammatory process and development of CD.