title: NOD2/CARD15 gene mutations in North Algerian patients with inflammatory bowel disease.
abstract: OBJECTIVE
  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.Arg(702)Trp, p.Gly908Arg and p.Leu(1007)fsinsC mutations) using the polymerase chain reaction-restriction fragment length polymorphism method. Allele and genotype frequencies in patients and control subjects were compared by χ(2) 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.Arg(702)Trp 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.Leu(1007)fsinsC 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.Leu(1007)fsinsC 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.
  
  
  CONCLUSIONS
  Further analyses are necessary to study genetic and environmental factors in IBD in the Algerian population, using larger patient groups.
authors.affiliation: 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.
authors.forename: Aziza
authors.initials: A
authors.lastname: Boukercha
authors.affiliation: 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.
authors.forename: Hamida
authors.initials: H
authors.lastname: Mesbah-Amroun
authors.affiliation: 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.
authors.forename: Amira
authors.initials: A
authors.lastname: Bouzidi
authors.affiliation: 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.
authors.forename: Houria
authors.initials: H
authors.lastname: Saoula
authors.affiliation: 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.
authors.forename: Mhamed
authors.initials: M
authors.lastname: Nakkemouche
authors.affiliation: 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.
authors.forename: Maryline
authors.initials: M
authors.lastname: Roy
authors.affiliation: 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.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.affiliation: 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.
authors.forename: Chafia
authors.initials: C
authors.lastname: Touil-Boukoffa
mesh_terms: D000293:Adolescent; D000328:Adult; D000462:Algeria / Q000453:epidemiology; D044383:Black People / Q000235:genetics; D016009:Chi-Square Distribution; D002648:Child; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D003424:Crohn Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: Algeria; Crohn’s disease; Inflammatory bowel disease; NOD2 mutations; Polymerase chain reaction-restriction fragment length polymorphism method; Ulcerative colitis