NOD2/CARD15, ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn's disease

World J Gastroenterol. 2010 Apr 14;16(14):1753-8. doi: 10.3748/wjg.v16.i14.1753.


Aim: To assess whether the polymorphisms of NOD2/CARD15, autophagy-related 16-like 1 (ATG16L1), and interleukin-23 receptor (IL23R) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn's disease (CD).

Methods: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15; rs2241880 A/G of ATG16L1, and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymorphism analysis. The polymorphisms rs2241880 A/G of the ATG16L1, and rs11209026 (R381Q) of the IL23R gene in the children's cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K).

Results: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without colonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to controls (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype.

Conclusion: Polymorphism 3020insC in NOD2/CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not early-onset disease.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Alleles
  • Autophagy-Related Proteins
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Child
  • Crohn Disease / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Greece
  • Humans
  • Male
  • Nod2 Signaling Adaptor Protein / genetics*
  • Polymorphism, Genetic
  • Receptors, Interleukin / genetics*
  • Young Adult


  • ATG16L1 protein, human
  • Autophagy-Related Proteins
  • Carrier Proteins
  • IL23R protein, human
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin