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

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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)
JournalNeurogastroenterology and Motility
Volume23
Issue number10
DOIs
StatePublished - Oct 2011

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Irritable Bowel Syndrome
Gastrointestinal Diseases
Genetic Predisposition to Disease
Inflammation
Crohn Disease
Genes
Phenotype
Genetic Models
Inflammatory Bowel Diseases
Mast Cells
Single Nucleotide Polymorphism
Interleukin-6
Alleles

Keywords

  • c11orf30
  • CDH1
  • ORMDL3
  • PRDM1
  • TLR9

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders : Preliminary analysis. / Camilleri, Michael; Carlson, P.; Mckinzie, S.; Zucchelli, M.; D'Amato, M.; Busciglio, I.; Burton, D.; Zinsmeister, A. R.

In: Neurogastroenterology and Motility, Vol. 23, No. 10, 10.2011.

Research output: Contribution to journalArticle

Camilleri, Michael ; Carlson, P. ; Mckinzie, S. ; Zucchelli, M. ; D'Amato, M. ; Busciglio, I. ; Burton, D. ; Zinsmeister, A. R. / Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders : Preliminary analysis. In: Neurogastroenterology and Motility. 2011 ; Vol. 23, No. 10.
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AU - Burton, D.

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AB - 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.

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