title: Functional Toll-Like Receptor (TLR)2 polymorphisms in the susceptibility to inflammatory bowel disease.
abstract: BACKGROUND
  The recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) suggest significant genetic overlap with complex mycobacterial diseases like tuberculosis or leprosy. TLR variants have previously been linked to susceptibility for mycobacterial diseases. Here we investigated the contribution to IBD risk of two TLR2 polymorphisms, the low-prevalence variant Arg753Gln and the GTn microsatellite repeat polymorphism in intron 2. We studied association with disease, possible correlations with phenotype and gene-gene interactions.
  
  
  RESULTS
  We conducted a large study in 843 patients with Crohn's disease, 426 patients with ulcerative colitis and 805 healthy, unrelated controls, all of European origin. Overall, the frequency for carriers of shorter GTn repeats in intron 2 of the TLR2 gene, which have previously been associated with low TLR2 expression and high IL-10 production, was slightly elevated in Crohn's disease and ulcerative colitis compared to healthy controls (16.0% resp. 16.7% vs. 12.8%). The highest frequency of short GTn carriers was noted among IBD patients on anti TNF-alpha therapy. However, none of these differences was significant in the multivariate analysis. The Arg753Gln polymorphism showed no association with any clinical subtype of IBD, including extensive colitis, for which such an association was previously described. We found no association with specific phenotypic disease subgroups. Also, epistasis analysis revealed no significant interactions between the two TLR2 variants and confirmed IBD susceptibility genes.
  
  
  CONCLUSIONS
  The two functional relevant polymorphisms in TLR2, the GTn microsatellite repeat polymorphism in intron 2 and the Arg753Gln variant do not seem to play a role in the susceptibility to Crohn's disease or ulcerative colitis.
authors.affiliation: Department of Medicine II, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Helga Paula
authors.identifier: http://orcid.org/0000-0002-6883-5034
authors.initials: HP
authors.lastname: Török
authors.affiliation: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology, Fontainebleau, France.|Institut Curie, Paris,France.|INSERM U900, Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Bellon
authors.affiliation: Department of Medicine II, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Konrad
authors.affiliation: Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lacher
authors.affiliation: Department of General, Visceral, Vascular and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Laurian
authors.initials: L
authors.lastname: Tonenchi
authors.affiliation: Department of General, Visceral, Vascular and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Siebeck
authors.affiliation: Department of Medicine II, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
authors.affiliation: Department of Medicine II, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Enrico Narciso
authors.initials: EN
authors.lastname: De Toni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2