Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease

Török, H.-P.; Glas, J.; Tonenchi, L.; Lohse, P.; Müller-Myhsok, B.; Limbersky, O.; Neugebauer, C.; Schnitzler, F.; Seiderer, J.; Tillack, C.; Brand, S.; Brünnler, G.; Jagiello, P.; Epplen, J. T.; Griga, T.; Klein, W.; Schiemonn, U.; Folwaczny, M.; Ochsenkühn, T.; Folwaczny, C.
October 2005
Gut;Oct2005, Vol. 54 Issue 10, p1421
Academic Journal
Background and aims: Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions. Patients and methods: The polymorphisms in DLG5 (113 G→A, 4136 C→A, and DLG5•e26), SLC22A4 (1672 C→T), and SLC2245(-207 G→C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD 15/NOD2 mutations was analysed. Results: No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR =1.65), which was even greater in the presence of CARD 15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non- fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery. Conclusion: Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.


Related Articles

  • Genetic Polymorphisms Associated With Inflammatory Bowel Disease Do Not Confer Risk for Primary Sclerosing Cholangitis. Karlsen, Tom H.; Hampe, Jochen; Wiencke, Kristine; Schrumpf, Erik; Thorsby, Erik; Lie, Benedicte A.; Broomé, Ulrika; Schreiber, Stefan; Boberg, Kirsten Muri // American Journal of Gastroenterology;Jan2007, Vol. 102 Issue 1, p115 

    OBJECTIVES: Approximately 80% of patients with primary sclerosing cholangitis (PSC) of Northern European origin have concurrent inflammatory bowel disease (IBD). The majority have ulcerative colitis, but there is also an association with Crohn's colitis. The pathogenetic link between PSC and IBD...

  • The Relationship Between Heritability and Smoking Habits in Crohn's Disease. Brignola, Corrado; Belloli, Clarissa; Ardizzone, Sandro; Astegiano, Marco; Cottone, Mario; Trallori, Giacomo // American Journal of Gastroenterology;Nov2000, Vol. 95 Issue 11, p3171 

    OBJECTIVE: In Crohn's disease (CD), the relationship between genetic predisposition and smoking has not been well defined. The aim of this study was to compare the smoking habits at the time of the diagnosis of CD patients having familial occurrence of inflammatory bowel disease (IBD) with those...

  • Contribution of NKX2-3 Polymorphisms to Inflammatory Bowel Diseases: A Meta-Analysis of 35358 subjects. XiaoCheng Lu; Linjun Tang; Kai Li; JinYu Zheng; Penglai Zhao; Yi Tao; Li-Xin Li // Scientific Reports;1/31/2014, p1 

    Polymorphisms in NKX2-3 gene have been inconsistently associated with Crohn's disease (CD) and ulcerative colitis (UC). To generate large-scale evidence on whether NKX2-3 polymorphisms are associated with CD or UC susceptibility we have conducted a meta-analysis of 17 studies involving 17329...

  • The CC chemokine receptor 5 Δ32 mutation is not associated with inflammatory bowel disease (IBD) in NE England. Craggs, A; Welfare, M; Donaldson, P T; Mansfield, J C // Genes & Immunity;Apr2001, Vol. 2 Issue 2, p114 

    Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract of unknown aetiology. Evidence of abnormalities in immune regulation and cytokine production in patients with IBD has led to investigations of various immuno-regulatory genes as potential...

  • Genetic Variants of Wnt Transcription Factor TCF-4 (TCF7L2) Putative Promoter Region Are Associated with Small Intestinal Crohn's Disease. Koslowski, Maureen J.; Kübler, Irmgard; Chamaillard, Mathias; Schaeffeler, Elke; Reinisch, Walter; Guoxing Wang; Beisner, Julia; Teml, Alexander; Peyrin-Biroulet, Laurent; Winter, Stefan; Herrlinger, Klaus R.; Rutgeerts, Paul; Vermeire, Séverine; Cooney, Rachel; Fellermann, Klaus; Jewell, Derek; Bevins, Charles L.; Schwab, Matthias; Stange, Eduard F.; Wehkamp, Jan // PLoS ONE;2009, Vol. 4 Issue 2, p1 

    Reduced expression of Paneth cell antimicrobial α-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of...

  • Factors associated with disease evolution in Greek patients with inflammatory bowel disease. Chatzicostas, Constantinos; Roussomoustakaki, Maria; Potamianos, Spiros; Paspatis, Gregorios; Mouzas, Ioannis; Romanos, John; Mavrogeni, Helen; Kouroumalis, Elias // BMC Gastroenterology;2006, Vol. 6, p21 

    Background: The majority of Crohn's disease patients with B1 phenotype at diagnosis (i.e. nonstricturing non-penetrating disease) will develop over time a stricturing or a penetrating pattern. Conflicting data exist on the rate of proximal disease extension in ulcerative colitis patients with...

  • Alteration of GI symptoms in a cow with Johne disease by the dietary organosulfur, 2-mercaptoethanol. Click, Robert E. // Virulence;Oct2012, Vol. 3 Issue 6, p543 

    Sub-phenotypes of inflammatory bowel disease (IBD)--Crohn disease, ulcerative colitis and some cases of irritable bowel syndrome--are generally considered a consequence of gastrointestinal inflammation of unknown etiology. Conventional therapy and more recently biologic agents, all with varying...

  • Novel Anti-Glycan Antibodies Related to Inflammatory Bowel Disease Diagnosis and Phenotype. Seow, Cynthia H.; Stempak, Joanne M.; Wei Xu; Hui Lan; Griffiths, Anne M.; Greenberg, Gordon R.; Steinhart, A. Hillary; Dotan, Nir; Silverberg, Mark S. // American Journal of Gastroenterology;Jun2009, Vol. 104 Issue 6, p1426 

    OBJECTIVES:We sought to evaluate whether two novel immunoglobulin A (IgA) cell wall polysaccharide antibodies, anti-laminarin (anti-L) and anti-chitin (anti-C), aid in the diagnosis and phenotype differentiation of Crohn's disease (CD) and ulcerative colitis (UC).METHODS:A cohort of 818...

  • Microaggregate of Immunostained Macrophages in Noninflamed Gastroduodenal Mucosa: A New Useful Histological Marker for Differentiating Crohn's Colitis From Ulcerative Colitis. Yao, Kenshi; Yao, Tsuneyoshi; Iwashita, Akinori; Matsui, Toshiyuki; Kamachi, Shino // American Journal of Gastroenterology;Aug2000, Vol. 95 Issue 8, p1967 

    OBJECTIVE: in 10% of cases it may be difficult to differentiate Crohn's colitis from ulcerative colitis. Distinguishing the two conditions is important because they are distinct entities with different therapeutic implications. Noncaseating granulomas are usually considered diagnostic of Crohn's...


Read the Article


Sign out of this library

Other Topics