Faculty Collaboration Database

Pediatric onset Crohn's colitis is characterized by genotype-dependent age-related susceptibility. Inflamm Bowel Dis 2007 Dec;13(12):1509-15

Date

09/01/2007

Pubmed ID

17763471

DOI

10.1002/ibd.20244

Scopus ID

2-s2.0-38049058330 (requires institutional sign-in at Scopus site)   54 Citations

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 x 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.

Author List

Levine A, Kugathasan S, Annese V, Biank V, Leshinsky-Silver E, Davidovich O, Kimmel G, Shamir R, Palmieri O, Karban A, Broeckel U, Cucchiara S

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Child
Crohn Disease
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Male
Nod2 Signaling Adaptor Protein
Polymorphism, Genetic
Time Factors