Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2015; 21(25): 7786-7794
Published online Jul 7, 2015. doi: 10.3748/wjg.v21.i25.7786
NOD2/CARD15 gene mutations in North Algerian patients with inflammatory bowel disease
Aziza Boukercha, Hamida Mesbah-Amroun, Amira Bouzidi, Houria Saoula, Mhamed Nakkemouche, Maryline Roy, Jean-Pierre Hugot, Chafia Touil-Boukoffa
Aziza Boukercha, Hamida Mesbah-Amroun, Amira Bouzidi, Chafia Touil-Boukoffa, Team Cytokines and NO Synthases, Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene, Algiers 16111, Algeria
Houria Saoula, Mhamed Nakkemouche, Department of Gastroenterology, Maillot University Hospital, Algiers 16111, Algeria
Maryline Roy, Jean-Pierre Hugot, Team Intestinal Inflammation, INSERM UMR1149, Xavier Bichat Faculty, Paris Diderot University, 75018 Paris, France
Jean-Pierre Hugot, Department of Gastroenterology, Robert Debré University Hospital, 75013 Paris, France
Author contributions: Boukercha A and Mesbah-Amroun H contributed equally to this work; Boukercha A, Mesbah-Amroun H, Nakkemouche M, Hugot JP and Touil-Boukoffa C designed the research; Boukercha A performed the research; Bouzidi A and Roy M contributed new reagents/analytic tools; Saoula H and Nakkemouche M treated patients and collected material and clinical data from patients; Boukercha A, Mesbah-Amroun H, Bouzidi A, Saoula H, Roy M and Hugot JP analyzed the data; Boukercha A and Mesbah-Amroun H wrote the paper; Hugot JP revised the article critically; Mesbah-Amroun H, Nakkemouche M, Hugot JP and Touil-Boukoffa C approved the final version to be published.
Supported by the Agence Thématique de la Recherche Scientifique en Santé, (ATRSS, ex ANDRS) (PNR N°37-ANDRS-2011).
Ethics approval: The study was reviewed and approved by the Ethics Committee of the Agence Thématique de la Recherche Scientifique en Santé (ATRSS, ex ANDRS).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Mesbah-Amroun Hamida has received research funding from the Agence Thématique de la Recherche Scientifique en Santé (ATRSS, ex ANDRS).
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author, Mesbah-Amroun H, at amrounhamida@yahoo.com or hamroun@usthb.dz. Consent was not obtained by participants for data sharing but the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hamida Mesbah-Amroun, PhD, Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene, BP32, Bab-Ezzouar, Algiers 16111, Algeria. amrounhamida@yahoo.com
Telephone: +213-7-79387611 Fax: +213-21-247217
Received: March 12, 2015
Peer-review started: March 13, 2015
First decision: March 26, 2015
Revised: April 23, 2015
Accepted: May 7, 2015
Article in press: May 7, 2015
Published online: July 7, 2015
Abstract

AIM: To analyse allelic frequency of NOD2 gene variants and to assess their correlation with inflammatory bowel disease (IBD) in Algeria.

METHODS: We studied 132 unrelated patients diagnosed with IBD, 86 with Crohn’s disease (CD) and 46 with ulcerative colitis (UC). Data was prospectively collected between January 2011 and December 2013. The demographic and clinical characteristics were recorded for all the patients. A group of 114 healthy unrelated individuals were selected as controls. All groups studied originated from different regions of North Algeria and confirmed the Algerian origin of their parents and grandparents. Informed and written consent was obtained from each of the participants. All individuals were genotyped for the three CD-associated NOD2 variants (p.Arg702Trp, p.Gly908Arg and p.Leu1007fsinsC mutations) using the polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies in patients and control subjects were compared by χ2 test and Fisher’s exact test where appropriate. Odds ratios (OR) and 95% confidence intervals (95%CI) were also estimated. Association analyses were performed to study the influence of these variants on IBD and on clinical phenotypes.

RESULTS: The p.Arg702Trp mutation showed the highest frequency in CD patients (8%) compared to UC patients (2%) (P = 0.09, OR = 3.67, 95%CI: 0.48-4.87) and controls (5%) (P = 0.4, OR = 1.47, 95%CI: 0.65-3.31). In CD patients allelic frequencies of p.Gly908Arg and p.Leu1007fsinsC variants compared to HC were 3% vs 2% (P = 0.5, OR = 1.67, 95%CI: 0.44-6.34); 2% vs 1% (P = 0.4 OR = 2.69 95%CI: 0.48-14.87 respectively). In UC patients, allelic frequencies of p.Gly908Arg and p.Leu1007fsinsC variants compared to HC were 1% vs 2% (P = 1, OR = 1.62, 95%CI: 0.17-4.74) and 2% vs 1% (P = 0.32, OR = 0.39, 95%CI: 0.05-2.87). The total frequency of the mutated NOD2 chromosomes was higher in CD (13%), than in HC (8%) and UC (5%). In addition, NOD2 variants were linked to a particular clinical sub-phenotype in CD in this Algerian cohort. As expected, the three NOD2 variants showed a significant association with CD but did not reach statistical significance, despite the fact that the allele frequency of NOD2 variants was in the range found in most of the European populations. This might be due to the non-exposure of the NOD2 carriers to environmental factors, required for the expression of the disease.

CONCLUSION: Further analyses are necessary to study genetic and environmental factors in IBD in the Algerian population, using larger patient groups.

Keywords: Algeria, Crohn’s disease, Ulcerative colitis, Inflammatory bowel disease, NOD2 mutations, Polymerase chain reaction-restriction fragment length polymorphism method

Core tip: We evaluated allelic frequency of NOD2 variants among 132 inflammatory bowel disease (IBD) patients and 114 unrelated healthy subjects from Algeria. Despite the fact that the frequency of NOD2 mutant alleles is in the range found in most of the European populations, we failed to demonstrate the association of these NOD2 variants with IBD susceptibility. This might be due to the non exposure of the NOD2 carriers to environmental factors, required for the expression of the disease. We can expect in the coming years to see an increased incidence of IBD associated with the spread of Western lifestyle in this region.