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NOD2/CARD15 Mutations among Bedouin Arabs with Inflammatory Bowel Disease: Frequency and Phenotype Correlation
Naim Abu Freha1, Wafi Badarna2, Muhammad Abu Tailakh3
1Departments of Gastroenterology and Hepatology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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 which 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 Crohn's disease than in ulcerative colitis 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 males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 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.
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