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

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 modif...

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Main Authors: Golshid Sanati, Mehrdad Noruzinia, Davood Jafari, Mohammad Ahmadvand, Shahram Teimourian, Naser Ebrahimi Daryani, Nima Rezaei
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2023-08-01
Series:Acta Medica Iranica
Subjects:
Online Access:https://acta.tums.ac.ir/index.php/acta/article/view/9867
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author Golshid Sanati
Mehrdad Noruzinia
Davood Jafari
Mohammad Ahmadvand
Shahram Teimourian
Naser Ebrahimi Daryani
Nima Rezaei
author_facet Golshid Sanati
Mehrdad Noruzinia
Davood Jafari
Mohammad Ahmadvand
Shahram Teimourian
Naser Ebrahimi Daryani
Nima Rezaei
author_sort Golshid Sanati
collection DOAJ
description 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.
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spelling doaj.art-dd31ecc92f804074a176fe80620cc0e02023-08-30T04:27:48ZengTehran University of Medical SciencesActa Medica Iranica0044-60251735-96942023-08-0161510.18502/acta.v61i5.13480Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s DiseaseGolshid Sanati0Mehrdad Noruzinia1Davood Jafari2Mohammad Ahmadvand3Shahram Teimourian4Naser Ebrahimi Daryani5Nima Rezaei6Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Division of Biomedical Sciences, School of Medicine, University of California, Riverside, USA 3 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Riverside, CA, USA.Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, IranDepartment of Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, IranDepartment of Internal Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, IranDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. ANDResearch Center for Immunodeficiencies, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran. AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. 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. https://acta.tums.ac.ir/index.php/acta/article/view/9867Nucleotide-binding oligomerization domain containing 2 (NOD2)Inflammatory bowel diseaseCrohn’s diseaseDNA methylation
spellingShingle Golshid Sanati
Mehrdad Noruzinia
Davood Jafari
Mohammad Ahmadvand
Shahram Teimourian
Naser Ebrahimi Daryani
Nima Rezaei
Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease
Acta Medica Iranica
Nucleotide-binding oligomerization domain containing 2 (NOD2)
Inflammatory bowel disease
Crohn’s disease
DNA methylation
title Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease
title_full Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease
title_fullStr Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease
title_full_unstemmed Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease
title_short Abnormal Promoter Methylation of Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) Gene in the Pathogenesis of Crohn’s Disease
title_sort abnormal promoter methylation of nucleotide binding oligomerization domain containing 2 nod2 gene in the pathogenesis of crohn s disease
topic Nucleotide-binding oligomerization domain containing 2 (NOD2)
Inflammatory bowel disease
Crohn’s disease
DNA methylation
url https://acta.tums.ac.ir/index.php/acta/article/view/9867
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