Nod2/Card15 Mutations Among Bedouin Arabs With Inflammatory Bowel Disease: Frequency And Phenotype Correlation

Background: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD.Objectives: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype.Methods: The IBD-Arab cohort in southern Israel included 68 patients, of whom 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC.Results: The NOD2/CARD15 mutation frequency was higher in CD than in UC patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 +/- 4.5 vs. 28.82 +/- 9.1 years (P = 0.04). All carriers were male, compared to 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 +/- 24.5 years compared to 41.2 +/- 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found.Conclusions: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.