Genotype-phenotype analysis of the CXCL16 p.Ala181Val polymorphism in inflammatory bowel disease

Clin Immunol. 2008 Apr;127(1):49-55. doi: 10.1016/j.clim.2007.11.016. Epub 2008 Jan 11.


To identify if genetic determinants of CXCL16 modulate the susceptibility and phenotype of inflammatory bowel diseases (IBD), we analyzed genomic DNA from 574 individuals (365 IBD patients, 209 healthy controls) for the CXCL16 p.Ala181Val polymorphism. In this study, we demonstrate that in Crohn's disease (CD), the CXCL16 p.Ala181Val polymorphism is not a disease susceptibility gene but associated with younger age at disease onset (p=0.016) and higher frequency of ileal involvement (p=0.024; OR 2.17; 95% CI 1.12-4.21) in ValVal carriers compared to a higher frequency of colonic involvement in AlaAla carriers (p=0.009; OR 2.60; CI 1.29-5.25). Carriers of at least one Val allele and one CARD15/NOD2 variant had a higher incidence of a stricturing and penetrating phenotype (p=0.030, OR 4.04, CI 1.27-12.84) and of stenoses (p=0.014; OR 3.97; CI 1.38-11.40) than patients carrying NOD2 variants only, suggesting that this polymorphism contributes to a severe disease phenotype in CD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Chemokine CXCL16
  • Chemokines, CXC / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / pathology
  • Male
  • Middle Aged
  • Mutation
  • Nod2 Signaling Adaptor Protein / genetics
  • Phenotype*
  • Polymorphism, Genetic*
  • Receptors, Scavenger / genetics*


  • CXCL16 protein, human
  • Chemokine CXCL16
  • Chemokines, CXC
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Scavenger