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CARD15 gene mutations and risk for early surgery in pediatric-onset Crohn's disease

Subra Kugathasan1, Nicole Collins, Karen Maresso

  • 1Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA. skuga@mcw.edu

Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association
|November 20, 2004
PubMed

Insights

Genetic CARD15 mutations, particularly 3020insC, are linked to earlier, more severe Crohn's disease in children, increasing the need for surgery. This finding aids in identifying at-risk pediatric patients.

Area of Science:

  • Genetics
  • Pediatric Gastroenterology
  • Inflammatory Bowel Disease

Background:

  • Crohn's disease (CD) risk is influenced by genetics.
  • Three CARD15 (NOD2) gene mutations are linked to adult-onset CD.
  • The impact of CARD15 mutations on pediatric CD is under investigation.

Purpose of the Study:

  • To examine the effect of CARD15 mutations on disease manifestation in childhood-onset CD.
  • To assess the influence of CARD15 mutations on disease progression and the risk of early surgery.
  • To determine if genetic factors predict surgical outcomes in pediatric Crohn's disease.

Main Methods:

  • Genotyping for three CARD15 mutations (R702W, G908R, 3020insC) in 186 children with CD.
  • Transmission-disequilibrium test for association with CD.
  • Logistic regression and Cox proportional hazard analysis for genotype-phenotype and surgical outcomes.

Main Results:

  • The 3020insC CARD15 mutation showed a significant association with CD (P = .0045).
  • Children with the 3020insC mutation had higher rates of ileal location (OR, 4.3) and stricturing disease (OR, 6.6).
  • The 3020insC mutation significantly increased the risk for earlier surgery (HR, 5.8; P < .0001).

Conclusions:

  • The 3020insC CARD15 variant influences early stricturing behavior and surgical resection in pediatric CD.
  • Ileal location and the 3020insC mutation are key factors in disease progression and surgical risk.
  • Genetic testing for CARD15 mutations can identify pediatric CD patients at high risk for early surgery.
Abstract

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