Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders: Preliminary analysis

M. Camilleri, P. Carlson, S. Mckinzie, M. Zucchelli, M. D'Amato, I. Busciglio, D. Burton, A. R. Zinsmeister

Research output: Contribution to journalArticle

34 Scopus citations

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. Key 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 48h. Specific tests for genetic interactions between loci revealed potential association of genes that influence neural, barrier, or mast cell function with colonic transit. Conclusions & Inferences Genetic variations that may influence local mucosal immune functions are univariately associated with altered colonic transit in lower FGID.

Original languageEnglish (US)
Pages (from-to)935-e398
JournalNeurogastroenterology and Motility
Volume23
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • CDH1
  • ORMDL3
  • PRDM1
  • TLR9
  • c11orf30

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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