Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease

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

doi:10.18502/acta.v61i5.13480

Golshid Sanati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Mehrdad Noruzinia Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Davood Jafari Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
Mohammad Ahmadvand Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Shahram Teimourian Department of Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Naser Ebrahimi Daryani Department of Internal Medicine, Imam Khomeini Hospital Complex, Tehran 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/acta.v61i5.13480

Keywords: Nucleotide-binding oligomerization domain containing 2 (NOD2); Inflammatory bowel disease; Crohn’s disease; DNA methylation

Abstract

Changes in the expression of nucleotide-binding oligomerization domain containing 2 (NOD2) play an important role in the pathogenesis of several autoimmune diseases, such as inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). It seems that epigenetic modifications, including DNA methylation, have an important role in the suppression of gene activity. In this study, the relationship between DNA methylation patterns of the promoter region of the NOD2 gene and the pathogenesis of CD was assessed. Colonic mucosal samples were obtained from 15 Iranian patients with CD and 15 matched healthy controls with no history of autoimmune diseases. After bisulfite conversion of genomic DNA, the DNA methylation status of three CpG sites in the promoter region of the NOD2 gene was determined by the real-time quantitative multiplex methylation-specific PCR assay. Using this approach, we identified a decreased level of methylation of the NOD2 promoter in the colonic mucosa of patients with CD (0.128±0.093 vs. 0.025±0.016, unmethylated DNA in CD vs. healthy controls, respectively, P<0.000). According to our findings, promoter hypomethylation of the NOD2 gene in the colonic mucosa might contribute to the development and severity of CD.