Association of NOD2/CARD15 variants with Crohn's disease in a Greek population

Maria Gazouli, Panayotis Zacharatos, Gerassimos J Mantzaris, Calypso Barbatis, Ioannis Ikonomopoulos, Athanassios J Archimandritis, John C Lukas, Efstathios Papalambros, Vassilis Gorgoulis
European Journal of Gastroenterology & Hepatology 2004, 16 (11): 1177-82

OBJECTIVE: Single nucleotide polymorphisms in the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease (CD), but whether this susceptibility extends to all ethnic groups and geographic areas remains unknown. The aim of the present study was to evaluate the NOD2/CARD15 mutations in Greek patients with CD.

METHODS: Individuals were genotyped for three NOD2/CARD15 mutations: R702W, G908R and L1007fsinsC. Blood samples were obtained from 120 patients with CD, 85 patients with ulcerative colitis, and 100 unrelated healthy controls.

RESULTS: Mutations in NOD2/CARD15 were observed with significantly greater frequency in CD patients (98/120, 81.7%) than in ulcerative colitis patients (40/85, 47%) (P < 0.0001) or in healthy individuals (21/100, 21%) (P < 0.0001). For CD patients, compared with controls, the odds were increased for carriage of the R702W (odds ratio, 12.25) and less for the G908R (odds ratio, 5.2) and L1007fsinsC (odds ratio, 3.9) mutations. The age of onset of CD was lower in Greek mutation carriers as compared with non-carriers of Greek origin (28.2 +/- 14.6 years versus 34 +/- 12.3 years, respectively; P = 0.036). Additionally, the frequency of NOD2/CARD15 mutations was increased in ileitis or ileocolitis compared with non-ileal disease.

CONCLUSIONS: The NOD2/CARD15 mutations are risk factors for CD in Greece, they appear to predict an earlier age of onset and are associated particularly with ileitis or ileocolitis.

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