Published online Jul 7, 2015. doi: 10.3748/wjg.v21.i25.7786
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
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.
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.