Gitit Tomer1, Clare Ceballos, Erlinda Concepcion, Keith J Benkov. 1. Division of Pediatric Gastroenterology and Nutrition, The Children's Inflammatory Bowel Disease Center, Mount Sinai School of Medicine, New York, New York, USA.
Abstract
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 (chi2=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 (chi2=4.5; p=0.03; OR=5; 95% CI=0.9-35.9). Of the children with NOD2/CARD15 variants, 44% were < or =5th percentile for weight at diagnosis, whereas only 15% of children without mutations were < or =5th percentile (chi2=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.
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 (chi2=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 (chi2=4.5; p=0.03; OR=5; 95% CI=0.9-35.9). Of the children with NOD2/CARD15 variants, 44% were < or =5th percentile for weight at diagnosis, whereas only 15% of children without mutations were < or =5th percentile (chi2=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.
Authors: Maria Gazouli; Ioanna Pachoula; Ioanna Panayotou; Gerassimos Mantzaris; George Chrousos; Nicholas P Anagnou; Eleftheria Roma-Giannikou Journal: World J Gastroenterol Date: 2010-04-14 Impact factor: 5.742
Authors: Josef Wagner; Winnie H Sim; Justine A Ellis; Eng K Ong; Anthony G Catto-Smith; Donald J S Cameron; Ruth F Bishop; Carl D Kirkwood Journal: PLoS One Date: 2010-11-08 Impact factor: 3.240
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