title: Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders: preliminary analysis.
abstract: BACKGROUND
  Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) coexist in some patients. We observed an association between Crohn's disease (CD) candidate gene TNFSF15 and IBS symptom phenotype. Three genes (TLR9, IL6, and CDH1) have been associated with postinfectious (PI)-IBS. Our aim was to preliminarily assess association between 30 susceptibility loci for CD, three genes associated with PI-IBS, and PARM1, with colonic transit in lower functional gastrointestinal disorders (FGID).
  
  
  METHODS
  A cohort of 665 persons was assembled in previous studies. TaqMan assay was used for all single nucleotide polymorphisms (SNPs) associated with the loci of interest. Data were analyzed for univariate associations with symptoms phenotype and colonic transit (nominal P values, uncorrected) using dominant and co-dominant genetic models.
  
  
  RESULTS
  Carriers of the rs5743836 risk allele had increased odds for IBS-D (vs control, P = 0.02, uncorrected). Among the CD risk loci, rs7927894 (P = 0.007), rs7746082 (P=0.011), rs2872507 (P = 0.014), together with rs5743836 (P = 0.010) were univariately associated with colonic transit at 24 or 48 h. Specific tests for genetic interactions between loci revealed potential association of genes that influence neural, barrier, or mast cell function with colonic transit.
  
  
  CONCLUSIONS
  Genetic variations that may influence local mucosal immune functions are univariately associated with altered colonic transit in lower FGID.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. camilleri.michael@mayo.edu
authors.forename: M
authors.initials: M
authors.lastname: Camilleri
authors.forename: P
authors.initials: P
authors.lastname: Carlson
authors.forename: S
authors.initials: S
authors.lastname: McKinzie
authors.forename: M
authors.initials: M
authors.lastname: Zucchelli
authors.forename: M
authors.initials: M
authors.lastname: D'Amato
authors.forename: I
authors.initials: I
authors.lastname: Busciglio
authors.forename: D
authors.initials: D
authors.lastname: Burton
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics* / Q000276:immunology; D005769:Gastrointestinal Motility / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide