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

Background: changes in the expression of nucleotide-binding oligomerization domain containing 2 (nod2) play an important role in the pathogenesis of a variety of autoimmune diseases including inflammatory bowel diseases (ibds). epigenetic modifications, including dna methylation, are considered an important mechanism in the suppression of gene activity. in this study, we investigated the relationship between dna methylation patterns of the promoter region of the nod2 gene and the pathogenesis of crohn’s disease (cd). methods: colonic mucosa samples were obtained from 15 iranian patients with ibd and 15 age- and sexmatched healthy controls with no history of autoimmune disease. after the 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 (qm-msp) assay. results: using this approach, we identified that ibd patients showed a decreased level of methylation of the nod2 promoter in the colonic mucosa than did the healthy controls. (unmethylated dna in crohn's disease vs. healthy controls; 0.128±0.093 vs. 0.025±0.016, p<0.000). conclusion: according to our findings, promoter hypomethylation of the nod2 gene in the colonic mucosa might contribute to the development and severity of cd. furthermore, aberrant dna methylation levels are expected to serve as a clinically useful risk marker.