Molecular basis of functional gastrointestinal disorders.
There are a number of abnormalities of gastrointestinal function, including sensory and motor dysfunction, which are believed to play a role in the manifestation of symptoms in patients with functional gastrointestinal disorders (FGID). In addition, there is a remarkable psychiatric comorbidity. Family and twin studies have provided strong evidence for a clustering of FGID in families and an increased concordance in monozygotic compared to dizygotic twins. This points towards the role of one or more hereditary (genetic) factors. Considering these disorders of function and the psychiatric comorbidity, polymorphisms of adrenergic, opioidergic or serotonergic receptors as well as G-protein beta3 (GNB3) subunit gene polymorphisms (C825T) and polymorphisms of 5-HT transporter genes are suitable causes. In addition, mediators or regulators of mucosal inflammation may trigger events that ultimately result in the manifestation of FGID. Thus, relevant polymorphisms of genes with immunmodulating and/or neuromodulating features (OPRM1, IL-4, IL-4R, TNFalpha) may also play a role in the manifestation of FGIDs.
Holtmann
Gerald
G
Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Essen, Hufelandstr 55, 45122 Essen, Germany. g.holtmann@uni-essen.de
Liebregts
Tobias
T
Siffert
Winfried
W
D000818:Animals; D015897:Comorbidity; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D005767:Gastrointestinal Diseases / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000523:psychology; D006801:Humans; D001523:Mental Disorders / Q000150:complications; D011110:Polymorphism, Genetic; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000502:physiology
D022702:Receptors, Adrenergic, beta-3; D019204:GTP-Binding Proteins