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Mechanisms of Disease: genetics of functional gastrointestinal disorders—searching the genes that matter

Nature Clinical Practice Gastroenterology & Hepatology volume 4, pages 102–110 (2007)Cite this article

Abstract

There is evidence to suggest that genetic factors contribute to the manifestation of functional gastrointestinal disorders (FGID). As such, it is important to note that FGID are heterogeneous; they have quite different clinical features and (probably) different underlying pathophysiologic mechanisms. Evidence from family and twin studies indicates that there is clustering of FGID in families and increased concordance in monozygotic compared with dizygotic twins. The clinical features of FGID implicate polymorphisms in the genes that encode adrenergic, opioidergic or serotonergic receptors, as well as in the G-protein β3 subunit (GNB3) gene and serotonin-transporter genes, in their manifestations. As mediators or regulators of mucosal inflammation can trigger events that ultimately result in manifestations of FGID, polymorphisms in genes that encode proteins with immunomodulatory and/or neuromodulatory features (e.g. OPRM1, IL4, IL4R, TNF) might also have a role in the manifestation of FGID. A two-step model for the role of genetic factors in the manifestation of functional gastrointestinal pain can, therefore, be proposed. In the presence of specific hereditary factors, environmental factors that do not usually cause long-term functional alterations are linked to the manifestation of symptoms.

Key Points

  • The pathogenesis of functional gastrointestinal disorders is probably multifactorial, and includes genetic and environmental factors

  • Polymorphisms of genes that encode cytokines and influence immune function are thought to contribute to the onset of symptoms in at least a subgroup of patients with irritable bowel syndrome

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Figure 1: The response of coronary blood flow to α2 adrenoceptor stimulation.
Figure 2: The proportion of individuals with the GNB3 CC genotype is significantly higher in patients who have multiple symptoms of functional gastrointestinal disorders (P <0.02).
Figure 3: A two-step model for the involvement of genetic factors in the pathophysiology of functional gastrointestinal disorders.

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Authors and Affiliations

  1. and G Holtmann is Director of the Department of Gastroenterology, B Adam and T Liebregts are Fellows, Hepatology and General Medicine, Royal Adelaide Hospital, University of Adelaide, Australia. All also work at the Nerve–Gut Research Laboratory, Hanson Institute, Adelaide, Australia.,

    Birgit Adam, Tobias Liebregts & Gerald Holtmann

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  1. Birgit Adam
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Correspondence to Gerald Holtmann.

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Adam, B., Liebregts, T. & Holtmann, G. Mechanisms of Disease: genetics of functional gastrointestinal disorders—searching the genes that matter. Nat Rev Gastroenterol Hepatol 4, 102–110 (2007). https://doi.org/10.1038/ncpgasthep0717

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