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 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 & INFERENCES: Genetic variations that may influence local mucosal immune functions are univariately associated with altered colonic transit in lower FGID.
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 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 & INFERENCES: Genetic variations that may influence local mucosal immune functions are univariately associated with altered colonic transit in lower FGID.
Authors: Alexandra-Chloé Villani; Mathieu Lemire; Marroon Thabane; Alexandre Belisle; Geneviève Geneau; Amit X Garg; William F Clark; Paul Moayyedi; Stephen M Collins; Denis Franchimont; John K Marshall Journal: Gastroenterology Date: 2010-01-04 Impact factor: 22.682
Authors: David K Breslow; Sean R Collins; Bernd Bodenmiller; Ruedi Aebersold; Kai Simons; Andrej Shevchenko; Christer S Ejsing; Jonathan S Weissman Journal: Nature Date: 2010-02-25 Impact factor: 49.962
Authors: N Manabe; B S Wong; M Camilleri; D Burton; S McKinzie; A R Zinsmeister Journal: Neurogastroenterol Motil Date: 2009-12-21 Impact factor: 3.598
Authors: A Deiteren; M Camilleri; A E Bharucha; D Burton; S McKinzie; A S Rao; A R Zinsmeister Journal: Neurogastroenterol Motil Date: 2009-12-18 Impact factor: 3.598
Authors: Dermot P B McGovern; Agnès Gardet; Leif Törkvist; Philippe Goyette; Jonah Essers; Kent D Taylor; Benjamin M Neale; Rick T H Ong; Caroline Lagacé; Chun Li; Todd Green; Christine R Stevens; Claudine Beauchamp; Phillip R Fleshner; Marie Carlson; Mauro D'Amato; Jonas Halfvarson; Martin L Hibberd; Mikael Lördal; Leonid Padyukov; Angelo Andriulli; Elisabetta Colombo; Anna Latiano; Orazio Palmieri; Edmond-Jean Bernard; Colette Deslandres; Daan W Hommes; Dirk J de Jong; Pieter C Stokkers; Rinse K Weersma; Yashoda Sharma; Mark S Silverberg; Judy H Cho; Jing Wu; Kathryn Roeder; Steven R Brant; L Phillip Schumm; Richard H Duerr; Marla C Dubinsky; Nicole L Glazer; Talin Haritunians; Andy Ippoliti; Gil Y Melmed; David S Siscovick; Eric A Vasiliauskas; Stephan R Targan; Vito Annese; Cisca Wijmenga; Sven Pettersson; Jerome I Rotter; Ramnik J Xavier; Mark J Daly; John D Rioux; Mark Seielstad Journal: Nat Genet Date: 2010-03-14 Impact factor: 38.330
Authors: Jeffrey C Barrett; James C Lee; Charles W Lees; Natalie J Prescott; Carl A Anderson; Anne Phillips; Emma Wesley; Kirstie Parnell; Hu Zhang; Hazel Drummond; Elaine R Nimmo; Dunecan Massey; Kasia Blaszczyk; Timothy Elliott; Lynn Cotterill; Helen Dallal; Alan J Lobo; Craig Mowat; Jeremy D Sanderson; Derek P Jewell; William G Newman; Cathryn Edwards; Tariq Ahmad; John C Mansfield; Jack Satsangi; Miles Parkes; Christopher G Mathew; Peter Donnelly; Leena Peltonen; Jenefer M Blackwell; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Nicholas Craddock; Panos Deloukas; Audrey Duncanson; Janusz Jankowski; Hugh S Markus; Christopher G Mathew; Mark I McCarthy; Colin N A Palmer; Robert Plomin; Anna Rautanen; Stephen J Sawcer; Nilesh Samani; Richard C Trembath; Anath C Viswanathan; Nicholas Wood; Chris C A Spencer; Jeffrey C Barrett; Céline Bellenguez; Daniel Davison; Colin Freeman; Amy Strange; Peter Donnelly; Cordelia Langford; Sarah E Hunt; Sarah Edkins; Rhian Gwilliam; Hannah Blackburn; Suzannah J Bumpstead; Serge Dronov; Matthew Gillman; Emma Gray; Naomi Hammond; Alagurevathi Jayakumar; Owen T McCann; Jennifer Liddle; Marc L Perez; Simon C Potter; Radhi Ravindrarajah; Michelle Ricketts; Matthew Waller; Paul Weston; Sara Widaa; Pamela Whittaker; Panos Deloukas; Leena Peltonen; Christopher G Mathew; Jenefer M Blackwell; Matthew A Brown; Aiden Corvin; Mark I McCarthy; Chris C A Spencer; Antony P Attwood; Jonathan Stephens; Jennifer Sambrook; Willem H Ouwehand; Wendy L McArdle; Susan M Ring; David P Strachan Journal: Nat Genet Date: 2009-11-15 Impact factor: 38.330
Authors: Michael Camilleri; Andrea Shin; Irene Busciglio; Paula Carlson; Andres Acosta; Adil E Bharucha; Duane Burton; Jesse Lamsam; Alan Lueke; Leslie J Donato; Alan R Zinsmeister Journal: Am J Physiol Gastrointest Liver Physiol Date: 2014-07-10 Impact factor: 4.052