title: Pediatric onset Crohn's colitis is characterized by genotype-dependent age-related susceptibility.
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.
authors.affiliation: Pediatric Gastroenterology Unit, Wolfson Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. alevine@wolfson.health.gov.il
authors.forename: Arie
authors.initials: A
authors.lastname: Levine
authors.forename: Subra
authors.initials: S
authors.lastname: Kugathasan
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
authors.forename: Vincent
authors.initials: V
authors.lastname: Biank
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
authors.forename: Ofir
authors.initials: O
authors.lastname: Davidovich
authors.forename: Gad
authors.initials: G
authors.lastname: Kimmel
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
authors.forename: Orazio
authors.initials: O
authors.lastname: Palmieri
authors.forename: Palmieri
authors.initials: P
authors.lastname: Orazio
authors.forename: Amir
authors.initials: A
authors.lastname: Karban
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
mesh_terms: D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic; D013997:Time Factors
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein