title: Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort.
abstract: BACKGROUND
  The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC.
  
  
  METHODS
  Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression.
  
  
  RESULTS
  The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59-6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64-5.32, p = 0.005).
  
  
  CONCLUSIONS
  Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC.
authors.affiliation: Medical Department, Viborg Regional Hospital, Viborg, Denmark.|Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Bank
authors.affiliation: Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.|Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Paal Skytt
authors.initials: PS
authors.lastname: Andersen
authors.affiliation: Department of Gastroenterology, Herlev Hospital, Herlev, Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Burisch
authors.affiliation: Department of Gastroenterology, Herlev Hospital, Herlev, Denmark.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pedersen
authors.affiliation: Department of Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Roug
authors.affiliation: Medical Department, Køge Hospital, Køge, Denmark.
authors.forename: Julied
authors.initials: J
authors.lastname: Galsgaard
authors.affiliation: Medical Department, Hillerød Hospital, Hillerød, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Ydegaard Turino
authors.affiliation: Medical Department, Sydvestjysk Hospital, Esbjerg, Denmark.|Department of medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Jacob Broder
authors.initials: JB
authors.lastname: Brodersen
authors.affiliation: Medical Department, Bispebjerg Hospital, Bispebjerg, Denmark.
authors.forename: Shaista
authors.initials: S
authors.lastname: Rashid
authors.affiliation: Medical Department, Nykøbing Falster Hospital, Nykøbing Falster, Denmark.
authors.forename: Britt
authors.initials: B
authors.lastname: Kaiser Rasmussen
authors.affiliation: Medical Department V, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Sara
authors.initials: S
authors.lastname: Avlund
authors.affiliation: Medical Department, Slagelse Hospital, Slagelse, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bastholm Olesen
authors.affiliation: Department of Respiratory Diseases B, Institute for Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Hoffmann
authors.affiliation: Biomedicine, University of Aarhus, Aarhus, Denmark.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Andersen Nexø
authors.affiliation: Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.|Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.|Department of Rheumatology, Frederiksberg Hospital, Frederiksberg, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Sode
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.affiliation: Medical Department, Viborg Regional Hospital, Viborg, Denmark.|Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.|Research unit for Molecular Diagnostic, Hospital of Southern Jutland Aabenraa, Aabenraa, Denmark.|OPEN Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
mesh_terms: D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D051193:Toll-Like Receptors