TITLE

Analysis of the IBD5 locus and potential gene-gene interactions in Crohn's disease

AUTHOR(S)
Negoro, K.; McGovern, D.P.B.; Kinouchi, Y.; Takahashi, S.; Lench, N.J.; Shimosegawa, T.; Carey, A.; Cardon, L.R.; Jewell, D.P.; van Heel, D.A.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003, Vol. 52 Issue 4, p541
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Genetic variation in the chromosome 5q31 cytokine cluster (IBD5 risk haplotype) has been associated with Crohn's disease (CD) in a Canadian population. We studied the IBD5 risk haplotype in both British and Japanese cohorts. Disease associations have also been reported for CARD15/NOD2 and TNF variants. Complex interactions between susceptibility loci have been shown in animal models, and we tested for potential gene-gene interactions between the three CD associated loci. Methods: Family based association analyses were performed in 457 British families (252 ulcerative colitis, 282 CD trios) genotyped for the IBD5 haplotype, common CARD15, and TNF-857 variants. To test for possible epistatic interactions between variants, transmission disequilibrium test analyses were further stratified by genotype at other loci, and novel log linear analyses were performed using the haplotype relative risk model. Case control association analyses were performed in 178 Japanese CD patients and 156 healthy controls genotyped for the IBD5 haplotype. Results: The IBD5 haplotype was associated with CD (p=0.007), but not with UC, in the British Caucasian population. The CARD15 variants and IBD5 haplotype showed additive main effects, and in particular no evidence for epistatic interactions was found. Variants from the IBD5 haplotype were extremely rare in the Japanese. Conclusions: The IBD5 risk haplotype is associated with British CD. Genetic variants predisposing to CD show heterogeneity and population specific differences.
ACCESSION #
9704749

 

Related Articles

  • IBD5 risk haplotype and CARD15 variants add up to a bigger chance of Crohn's disease.  // Journal of Medical Genetics;Nov2003, Vol. 40 Issue 11, p831 

    Shows that the 5q31 cytokine cluster in British Caucasians does not interact with CARD15 variants. Conduction of genetic studies on the susceptibility to Crohn's disease; Linkage disequilibrium of IBD5 haplotype with CD phenotype; Performance of stratified transmission disequilibrium tests.

  • The Pathogenesis of Mucosal Inflammation in Murine Models of Inflammatory Bowel Disease and Crohn Disease. Strober, Warren; Lúdvíksson, Björn R.; Fuss, Ivan J. // Annals of Internal Medicine;05/15/98, Vol. 128 Issue 10, p848 

    Presents information on mucosal inflammation, with reference to the inflammatory bowel disease and Crohn disease. Discussion on the over-production of Th1 cytokines interleukin-12 and interferon-...; Resemblance of models of intestinal inflammation to Crohn disease; Treatment of the Crohn disease.

  • Combined Polymorphisms in Genes Encoding the Inflammasome Components NALP3 and CARD8 Confer Susceptibility to Crohn's Disease in Swedish Men. Schoultz, Ida; Verma, Deepti; Halfvarsson, Jonas; Törkvist, Leif; Fredrikson, Mats; Sjöqvist, Urban; Lördal, Mikael; Tysk, Curt; Lerm, Maria; Söderkvist, Peter; Söderholm, Johan D. // American Journal of Gastroenterology;May2009, Vol. 104 Issue 5, p1180 

    OBJECTIVES:Crohn's disease (CD) is characterized by overproduction of proinflammatory cytokines like interleukin (IL)-1β. Production of mature IL-1β is dependent on a caspase-1-activatingprotein complex called the NALP3 inflammasome, composed of NALP3, ASC, and CARD8. NALP3 shares...

  • Integrating Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease: Current and Future Perspectives. Blam, Michael E.; Stein, Robert B.; Lichtenstein, Gary R. // American Journal of Gastroenterology;Jul2001, Vol. 96 Issue 7, p1977 

    Crohn's disease and ulcerative colitis are two idiopathic inflammatory disorders of the GI tract. Manifestations of disease can be severe and lead to long term therapy with a variety of medications and/or surgery. Standard medical therapy consists of agents that either treat suppurative...

  • Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-γ axis. Kamada, Nobuhiko; Hisamatsu, Tadakazu; Okamoto, Susumu; Chinen, Hiroshi; Kobayashi, Taku; Sato, Toshiro; Sakuraba, Atsushi; Kitazume, Mina T.; Sugita, Akira; Koganei, Kazutaka; Akagawa, Kiyoko S.; Hibi, Toshifumi // Journal of Clinical Investigation;Jun2008, Vol. 118 Issue 6, p2269 

    Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified...

  • Cytokine and Anti-cytokine Therapies for Inflammatory Bowel Disease. Ogata, Haruhiko; Hibi, Toshifumi // Current Pharmaceutical Design;May2003, Vol. 9 Issue 14, p1107 

    Although the pathogenesis of inflammatory bowel disease (IBD) remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of anti-inflammatory...

  • Probiotics, Immune Function, Infection and Inflammation: A Review of the Evidence from Studies Conducted in Humans. Lomax, A. R.; Calder, P. C. // Current Pharmaceutical Design;5/1/2009, Vol. 15 Issue 13, p1428 

    A number of studies have been performed examining the influence of various probiotic organisms, either alone or in combination, on immune parameters, infectious outcomes, and inflammatory conditions in humans. Some components of the immune response, including phagocytosis, natural killer cell...

  • Role of Dlg5/lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-Mesenchymal Transition in LLc-PK1 Renal Epithelial Cells. Sezaki, Takuhito; Inada, Kohki; Sogabe, Takayuki; Kakuda, Kumiyo; Tomiyama, Lucia; Matsuno, Yohsuke; Ichikawa, Takafumi; Matsuo, Michinori; Ueda, Kazumitsu; Kioka, Noriyuki // PLoS ONE;Apr2012, Vol. 7 Issue 4, p1 

    Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase adaptor family of proteins, some of which are involved in the regulation of epithelial-to-mesenchymal transition (EMT). Dlg5 has been described as a susceptibility gene for Crohn's disease; however, the...

  • Perianal Crohn's disease and infliximab therapy. McNamara, D. A.; Brophy, S.; Hyland, J. M. P. // Surgeon (Edinburgh University Press);Oct2004, Vol. 2 Issue 5, p258 

    Introduction: Perianal manifestations occur in almost half of patients with Crohn's disease and often respond poorly to conventional therapies. The introduction of anti-tumour necrosis factor alpha agents (e.g. infliximab) has altered the management of patients who fail first and second line...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics