Michael Camilleri1. 1. Clinical Enteric Neuroscience Translational and Epidemiological Research, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA. camilleri.michael@mayo.edu
Abstract
PURPOSE: Familial aggregation and sibling pair studies suggest there is a genetic contribution to the development of irritable bowel syndrome (IBS). The aim of this study was to review the evidence of genetics in IBS based on genetic epidemiology, studies of association with intermediate phenotypes and pharmacogenetics. RESULTS: Genetic association studies with IBS symptom phenotype have generally provided inconsistent results for many candidate genes investigated, such as SLC6A4, GNB3, and IL-10. There have been no genome-wide association studies in IBS to date. Studies of associations of candidate genes with intermediate phenotypes suggest associations with pathophysiological mechanisms of motor and sensory functions; however, these results also require replication. Pharmacogenetics studies illustrate the potential of genetics to impact on response to therapy, as observed with SLC6A4 and responses to the 5-HT3 antagonist alosetron and the 5-HT4 agonist, tegaserod. CONCLUSIONS: While the heritable component and genetics in the complex disorder of IBS are still poorly understood, studies of the associations of spontaneous genetic variations and altered functions may provide novel insights of the mechanisms contributing to the disease.
PURPOSE:Familial aggregation and sibling pair studies suggest there is a genetic contribution to the development of irritable bowel syndrome (IBS). The aim of this study was to review the evidence of genetics in IBS based on genetic epidemiology, studies of association with intermediate phenotypes and pharmacogenetics. RESULTS: Genetic association studies with IBS symptom phenotype have generally provided inconsistent results for many candidate genes investigated, such as SLC6A4, GNB3, and IL-10. There have been no genome-wide association studies in IBS to date. Studies of associations of candidate genes with intermediate phenotypes suggest associations with pathophysiological mechanisms of motor and sensory functions; however, these results also require replication. Pharmacogenetics studies illustrate the potential of genetics to impact on response to therapy, as observed with SLC6A4 and responses to the 5-HT3 antagonist alosetron and the 5-HT4 agonist, tegaserod. CONCLUSIONS: While the heritable component and genetics in the complex disorder of IBS are still poorly understood, studies of the associations of spontaneous genetic variations and altered functions may provide novel insights of the mechanisms contributing to the disease.
Authors: Kersten M Small; Lynne E Wagoner; Albert M Levin; Sharon L R Kardia; Stephen B Liggett Journal: N Engl J Med Date: 2002-10-10 Impact factor: 91.245
Authors: H J Kim; M Camilleri; P J Carlson; F Cremonini; I Ferber; D Stephens; S McKinzie; A R Zinsmeister; R Urrutia Journal: Gut Date: 2004-06 Impact factor: 23.059
Authors: Ruth Kohen; Monica E Jarrett; Kevin C Cain; Sang-Eun Jun; Grace P Navaja; Sarah Symonds; Margaret M Heitkemper Journal: Dig Dis Sci Date: 2009-12 Impact factor: 3.199
Authors: Timothy G Dinan; John Cryan; Fergus Shanahan; P W Napoleon Keeling; Eamonn M M Quigley Journal: Nat Rev Gastroenterol Hepatol Date: 2010-06-29 Impact factor: 46.802
Authors: Michael Camilleri; Eric W Klee; Andrea Shin; Paula Carlson; Ying Li; Madhusudan Grover; Alan R Zinsmeister Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-11-07 Impact factor: 4.052
Authors: Banny S Wong; Michael Camilleri; Paula J Carlson; Maria E Guicciardi; Duane Burton; Sanna McKinzie; Archana S Rao; Alan R Zinsmeister; Gregory J Gores Journal: Gastroenterology Date: 2011-03-09 Impact factor: 22.682
Authors: D P Graham; L Savas; D White; R El-Serag; S Laday-Smith; G Tan; H B El-Serag Journal: Aliment Pharmacol Ther Date: 2009-10-08 Impact factor: 8.171