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

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Inflammatory Bowel Diseases

Volume 13, Issue 12 , Pages 1509 - 1515

Original Article

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

Arie Levine, MD 1 *, Subra Kugathasan, MD 2, Vito Annese, MD 3, Biank, MD 1, Esther Leshinsky-Silver, PhD 4, Ofir ovich, MD 5, Gad Kimmel, MD, PhD 5, Ron Shamir, PhD 5, Palmieri Orazio, PhD 3, Amir Karban, MD 6, Ulrich Broeckel, MD 2, Salvatore Cucchiara, MD 7

1Pediatric Gastroenterology Unit, Wolfson Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel2Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin3Gastroenterology and Molecular Biology Laboratory, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy4Molecular Biology Laboratory, Wolfson Medical Center, Holon, Israel5School of Computer Science, Tel Aviv University, Tel Aviv, Israel6Gastroenterology Division, Rambam Medical Center, Haifa, Israel7Pediatric Gastroenterology Unit, University of Rome La Sapienza, Rome, Italy

email: Arie Levine (alevine@...)

*Correspondence to Arie Levine, Pediatric Gastroenterology Unit, Wolfson Medical Center, POB 5 Holon, Israel, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Keywords

Crohn's disease • inflammatory bowel disease • child • phenotype • genes • colitis • NOD2

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.

(Inflamm Bowel Dis 2007)

Received: 12 February 2007; Accepted: 6 July 2007

Digital Object Identifier (DOI)