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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 127; no. 1; pp. 49 - 55
• Main Authors: Seiderer, Julia, Dambacher, Julia, Leistner, Dorothea, Tillack, Cornelia, Glas, Jürgen, Niess, Jan-Hendrik, Pfennig, Simone, Jürgens, Matthias, Müller-Myhsok, Bertram, Göke, Burkhard, Ochsenkühn, Thomas, Lohse, Peter, Reinecker, Hans-Christian, Brand, Stephan
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.04.2008; Elsevier
• Subjects: Adult; Age of Onset; Allergy and Immunology; Biological and medical sciences; CARD15; Chemokine; Chemokine CXCL16; Chemokines, CXC - genetics; Crohn's disease; CXCL16; CXCR6; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genetic Predisposition to Disease; Genetics; Genotype; Humans; Inflammatory bowel disease; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - pathology; Intestinal inflammation; Male; Medical sciences; Middle Aged; Mutation; Nod2 Signaling Adaptor Protein - genetics; Other diseases. Semiology; Phenotype; Polymorphism; Polymorphism, Genetic; Receptors, Scavenger - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Ulcerative colitis; frameshift; GALT; antigen-presenting cell; IBD; odds ratio; CXCR6; fs; TNF; LPS; UC; CARD; CXCL16; nucleotide-binding oligomerization domain; Intestinal inflammation; Genetics; ulcerative colitis; TLR; interleukin; natural killer cell; wt; caspase-activation recruitment domain; Toll-like receptor; CD; NOD; IL; OR; tumour necrosis factor-alpha-converting enzyme; TACE; Crohn's disease; inflammatory bowel disease; versus; mAb; Chemokine; APC; tumor necrosis factor; gut-associated lymphoid tissue; CARD15; lipopolysaccharide; monoclonal antibody; wild-type; NK; vs; dendritic cell; DC; Polymorphism; Inflammatory bowel disease; Ulcerative colitis; Typing; Digestive system; Gut; Genotype; Inflammation; Inflammatory disease; Crohn disease; Phenotype; Immunology; CXCL16: CXCR6; Digestive diseases; Intestinal disease; Intestinal inflammation CARD15
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2007.11.016

Abstract 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.