Specific association of a CLEC16A/KIAA0350 polymorphism with NOD2/CARD15(-) Crohn's disease patients

Eur J Hum Genet. 2009 Oct;17(10):1304-8. doi: 10.1038/ejhg.2009.50. Epub 2009 Apr 1.


Independent genome-wide association studies highlighted the function of CLEC16A/KIAA0350 polymorphisms modifying the risk to either multiple sclerosis (rs6498169) or type 1 diabetes (rs2903692). This C-type lectin gene maps to a linkage disequilibrium block at 16p13 and a functional role of this gene could be envisaged for other immune-related conditions, such as inflammatory bowel disease (IBD). The present study, aimed at investigating the association of those two polymorphisms with IBD, included 720 IBD patients and 550 ethnically matched healthy controls. The effect of rs2903692 previously described in diabetes was observed specifically for Crohn's disease (CD) patients lacking the main susceptibility factor described to date, that is, three polymorphisms within another pattern recognition gene, NOD2/CARD15 (NOD2(-) vs NOD2(+) CD patients, G vs A: P=0.008; OR (95% CI)=1.54 (1.10-2.15); NOD2(-) CD patients vs controls: P=0.008; OR (95% CI)=1.37 (1.08-1.73)). Replication of these findings was performed in independent Spanish cohorts of 544 IBD patients and 340 controls and the combined data yielded significant differences (405 NOD2(-) vs 204 NOD2(+) CD patients, G vs A: P=0.0012; OR(M-H) (95% CI)=1.49 (1.17-1.90); NOD2(-) CD patients vs controls: P=0.0007; OR(M-H) (95% CI)=1.35 (1.13-1.60)). The pooled analysis of the ulcerative colitis patients vs controls also yielded a significant risk (P=0.0005; OR (95% CI)=1.52 (1.19-1.93)). These data would suggest that microbial recognition through different pathways seems to converge in the development of these polygenic bowel diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cohort Studies
  • Crohn Disease / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Lectins / genetics
  • Lectins, C-Type / genetics*
  • Linkage Disequilibrium
  • Monosaccharide Transport Proteins / genetics*
  • Multiple Sclerosis / genetics
  • Nod2 Signaling Adaptor Protein / genetics*
  • Odds Ratio
  • Polymorphism, Genetic*
  • Spain


  • CLEC16A protein, human
  • Lectins
  • Lectins, C-Type
  • Monosaccharide Transport Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein