CARD15 and HLA DRB1 Alleles Influence Susceptibility and Disease Localization in Crohn's Disease

Newman, Bill; Silverberg, Mark S.; Xiangjun Gu; Qing Zhang; Lazaro, Ana; Steinhart, A. Hillary; Greenberg, Gordon R.; Griffiths, Anne M.; McLeod, Robin S.; Cohen, Zane; Fernández-Viña, Marcelo; Amos, Christopher I.; Siminovitch, Katherine
February 2004
American Journal of Gastroenterology;Feb2004, Vol. 99 Issue 2, p306
Academic Journal
OBJECTIVES: Crohn's disease (CD) is a chronic inflammatory disease of the gut associated with allelic variants of CARD15 and HLA-DRB1 genes. We investigated the prevalence and effects of these variants in a Canadian CD cohort.METHODS: 507 unrelated CD patients were genotyped for the three major CD-associated variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) and for thirteen HLA-DRB1 alleles.RESULTS: At least one CARD15 variant was present in 32.5% of the CD patients compared with 20% of controls. The prevalence of CARD15 mutation was similar in both sporadic and familial and Jewish and non-Jewish CD patients. The Gly908Arg variant was significantly higher and the Arg702Trp variant significantly lower in Jewish compared to non-Jewish patients. A positive association between the HLA-DRB1*0103 allele and CD was detected in non-Jewish, familial cases (p= 0.0002), with risk for CD increased by 6.7 fold by the presence of an HLA-DRB1*0103 allele as compared to 1.9 fold and 19 fold by a single or two CARD15 variant alleles, respectively. We show a significant association of ileal involvement with CARD15 variants (OR= 1.8;p= 0.02), HLA-DRB1*0701 (OR= 1.9;p= 0.006) and DRB1*04 (OR= 1.7;p= 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients. By contrast, the HLA-DRB1*0103 allele was associated with later age of diagnosis (p= 0.02) and pure colonic disease (p= 0.000013).These observations confirm the influence of CARD15 and HLA-DRB1 alleles on both CD susceptibility and site of disease and identify genotyping of these variants as a potential tool for improved diagnosis and risk prediction in CD.


Related Articles

  • SEQUENCE VARIATION IN THE CARD15 (NOD2) GENE AND SUSCEPTIBILITY TO CROHN'S DISEASE. King, K.; Onnie, C.; Mirza, M.; Fisher, S.; Cuthbert, A.; Sanderson, S.; Forbes, A.; Mansfield, J.; Lewis, C.; Mathew, C. // Gut;Apr2003 Supplement 1, Vol. 52, pA60 

    Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is a complex disorder, with both genetic and environmental aetiology. Three sequence variants in the CARD15 gene have recently been shown to be associated with susceptibility to CD. There is also evidence of an excess of rare...

  • The Role of Genetics in Inflammatory Bowel Disease. Henckaerts, Liesbet; Figueroa, Carolina; Vermeire, Séverine; Sans, Miquel // Current Drug Targets;May2008, Vol. 9 Issue 5, p361 

    The volume of research undertaken on the genetic susceptibility of inflammatory bowel disease (IBD) has been tremendous. Genome-wide linkage studies pointed towards more than 10 chromosomal regions and fine-mapping of these regions led to the identification of a number of genes, including CARD15...

  • A Subgroup of First-Degree Relatives of Crohn's Disease Patients Shows a Profile of Inflammatory Markers in the Blood Which Is More Typical of Crohn's Disease Patients Than of Normal Individuals. Efrat, Broide; Iris, Goren; Wang, Hongbin; Eitan, Scapa; Yona, Keisari // Mediators of Inflammation;4/1/2006, Vol. 2006 Issue 2, p1 

    Introduction. Family member with IBD is the greatest risk factor for developing the disease. The hematological profile of first-degree relatives (FDRs) of Crohn's disease (CD) patients was studied in order to identify healthy FDRs at risk to develop disease. Materials and methods. Thirty CD...

  • Inflammatory bowel disease posters.  // Gut;Apr2005 Supplement 2, Vol. 54, pA89 

    The article presents information on abstracts related to inflammatory bowel disease. An abstract presents information on the faecal calprotectin in the management of IBD and in the assessment of patients with LBS. Calprotectin is a neutrophil derived protein that is stable in stool. It shows...

  • Inflammatory bowel disease: past, present, and future. Sands, Bruce E. // Journal of Gastroenterology;Jan2007, Vol. 42 Issue 1, p16 

    Crohn's disease and ulcerative colitis, collectively known as the inflammatory bowel diseases (IBD), are largely diseases of the twentieth century, and are associated with the rise of modern, Westernized industrial society. Although the causes of these diseases remain incompletely understood,...

  • Neuroinflammation in inflammatory bowel disease. Lakhan, Shaheen E.; Kirchgessner, Annette // Journal of Neuroinflammation;2010, Vol. 7, p37 

    Inflammatory bowel disease is a chronic intestinal inflammatory condition, the pathology of which is incompletely understood. Gut inflammation causes significant changes in neurally controlled gut functions including cramping, abdominal pain, fecal urgency, and explosive diarrhea. These symptoms...

  • Can Calprotectin Predict Relapse Risk in Inflammatory Bowel Disease? D'Inc, Renata; Dal Pont, Elisabetta; Di Leo, Vincenza; Benazzato, Luca; Martinato, Matteo; Lamboglia, Francesca; Oliva, Lydia; Carlo Sturniolo, Giacomo // American Journal of Gastroenterology;Aug2008, Vol. 103 Issue 8, p2007 

    OBJECTIVE: Assessing the clinical course of inflammatory bowel disease (IBD) patients consists of periodical clinical evaluations and laboratory tests. We aimed to assess the role of calprotectin tests in predicting clinical relapse in IBD patients. METHODS: Ninety-seven patients with ulcerative...

  • Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy. Torres, M. I.; Riós, A.; A. Crusius, J. Bart // World Journal of Gastroenterology;4/7/2008, Vol. 14 Issue 13, p1972 

    Although the aetiology of inflammatory bowel disease (IBD) remains unknown, the pathogenesis is gradually being unravelled, seeming to be the result of a combination of environmental, genetic, and immunological factors in which an uncontrolled immune response within the intestinal lumen leads to...

  • Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease. Ward, L. M.; Rauch, F.; Matzinger, M. A.; Benchimol, E. I.; Boland, M.; Mack, D. R. // Osteoporosis International;Feb2010, Vol. 21 Issue 2, p331 

    Children with inflammatory bowel disease (IBD) manifest low bone mass; the cause remains unclear. We performed transilial bone biopsies in 20 IBD children at diagnosis and found a mild cortical bone deficit and slow bone turnover. It is possible that low mechanical stimulation due to inadequate...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics