NOD2/CARD15 Variants Are Associated with Lower Weight at Diagnosis in Children with Crohn's Disease

OBJECTIVES: NOD2/CARD15 variants have recently been shown to be associated with Crohn's disease (CD). No analysis of NOD2/CARD15 gene variants has so far been reported in pediatric patients. Therefore, our aim was to analyze NOD2/CARD15 gene variants in children with CD and to perform genotype-phenotype analyses. METHODS: We studied 101 children with CD and 136 healthy controls. Detailed phenotypic information was obtained from each patient. Patients were genotyped for the three NOD2/CARD15 variants R702W (single nucleotide polymorphism 8 [SNP8]), G908R (SNP12), and L1007fs (SNP13), and genotype-phenotype correlations were performed. RESULTS: We found 33 NOD2/ CARD15 mutations in 29 of 101 patients (29%). The frequency of NOD2 variation was 31% in white (n = 87) compared with 11% in controls (χ² = 14; p = 0.0001; OR = 3.7; 95% CI = 1.7-7.8). Four white patients but not control subjects were compound heterozygotes. NOD2/CARD15 variants were significantly associated with ileal disease (χ² = 4.5; p = 0.03; OR = 5; 95% CI = 0.9-35.9). Of the children with NOD2/CARD 15 variants, 44% were ≤5th percentile for weight at diagnosis, whereas only 15% of children without mutations were ≤5th percentile (χ² = 8.7; p = 0.003; OR = 4.5; 95% CI = 1.4-14.4). Similar trends were observed for height but they did not reach statistical significance. CONCLUSIONS: Our results demonstrate that: 1) the three NOD2/CARD15 variants confer risk to CD in children; 2) NOD2/CARD15 variants are associated with ileal disease in children as in adults; and 3) NOD2/CARD15 variants are associated with lower weight percentiles at diagnosis in children and a tendency toward lower height percentile, suggesting an association between growth in children with CD.