Pediatric onset crohn's colitis is characterized by genotype-dependent age-related susceptibility

Arie Levine, Subra Kugathasan, Vito Annese, Vincent Biank, Esther Leshinsky-Silver, Ofir Davidovich, Gad Kimmel, Ron Shamir, Palmieri Orazio, Amir Karban, Ulrich Broeckel, Salvatore Cucchiara

Research output: Contribution to journalArticle

Abstract

Background: Pediatric onset Crohn's disease (CD) is associated with more colitis and less ileitis compared with adult onset CD. Differences in disease site by age may suggest a different genotype, or different host responses such as decreased ileal susceptibility or increased susceptibility of the colon. Methods: We evaluated 721 pediatric onset CD patients from 3 cohorts with a high allele frequency of NOD2/CARD15 mutations. Children with isolated upper intestinal disease were excluded. The remaining 678 patients were evaluated for interactions between age of onset, NOD2/CARD15, and disease location. Results: We found an age-related tendency for isolated colitis. Among pediatric onset patients without NOD2/CARD15 mutations, colitis without ileal involvement was significantly more common in first-decade onset patients (P = 4.57 × 10 -5, odds ratio [OR] 2.76, 95% confidence interval [CI] 1.72-4.43). This was not true for colonic disease with ileal involvement (P = 0.35), or for isolated colitis in patients with NOD2/CARD15 mutations (P = 0.61). Analysis of 229 patients with ileal or ileocolonic disease and a NOD2/CARD15 mutation disclosed that ileocolitis was more prevalent through age 10, while isolated ileitis was more prevalent above age 10 (P = 0.016). NOD2/CARD15 mutations were not associated with age of onset. Conclusions: In early-onset pediatric CD, children with NOD2/CARD15 mutations demonstrate more ileocolitis and less isolated ileitis. Young children without NOD2/CARD15 mutations have an isolated colonic disease distribution, suggesting that this phenotype is associated with genes that lead to a specific phenotype of early-onset disease.

Original languageEnglish
Pages (from-to)1509-1515
Number of pages7
JournalInflammatory Bowel Diseases
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Child
  • Colitis
  • Crohn's disease
  • Genes
  • Inflammatory bowel disease
  • NOD2
  • Phenotype

ASJC Scopus subject areas

  • Gastroenterology

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    Levine, A., Kugathasan, S., Annese, V., Biank, V., Leshinsky-Silver, E., Davidovich, O., Kimmel, G., Shamir, R., Orazio, P., Karban, A., Broeckel, U., & Cucchiara, S. (2007). Pediatric onset crohn's colitis is characterized by genotype-dependent age-related susceptibility. Inflammatory Bowel Diseases, 13(12), 1509-1515. https://doi.org/10.1002/ibd.20244