NOD2 mutations predict the risk for surgery in pediatric-onset Crohn's disease

作者：Lacher Martin^*; Helmbrecht Johanna; Schroepf Sebastian; Koletzko Sibylle; Ballauff Antje; Classen Martin; Uhlig Holm; Hubertus Jochen; Hartl Dominik; Lohse Peter; von Schweinitz Dietrich; Kappler Roland

来源：Journal of Pediatric Surgery, 2010, 45(8): 1591-1597.

DOI：10.1016/j.jpedsurg.2009.10.046

• Crohn disease
• Inflammatory bowel disease
• NOD2
• CARD15
• Mutation
• p.1007fs
• Strictures
• Surgery

Backgroud/Purpose: Three common mutations of the NOD2/CARD15 gene have been associated with Crohn disease (CD), ileal disease location, and fibrostenotic behavior. The aim of this study was to investigate the effect of these mutations on disease manifestation and the risk of surgery in a cohort of German childhood-onset CD patients.
Methods: Genotyping for the NOD2 mutations p.Arg702Trp, p.Gly908Arg, and p.1007fs was performed in 171 CD children (onset of disease <17 years; mean 11.8 years) and in 253 controls. NOD2 mutation status was correlated with the need for surgery during childhood.
Results: Seventy-eight children (45.6%) were carriers of at least 1 NOD2 mutation versus 36 (14.2%) in the control group (P < .0001). NOD2 mutations were highly associated with CD and stricturing behavior (P < .0001), with the p.1007fs mutation also conferring a risk for isolated ileal disease (P = .003). Thirty-two children (18.7%) needed an intestinal resection with a significant association between the need of surgery and NOD2 carrier status. Surgery occurred at an earlier stage of disease in children with p.1007fs mutations.
Conclusions: In children with pediatric-onset CD, the need for surgical therapy younger than 17 years is associated with the NOD2 genotype. Genetic testing therefore may identify children with CD who are at risk.

• 出版日期2010-8