Genetic contributions to the pathogenesis of functional dyspepsia

GNB3, CCK-AR, IL-17F, and IL-10 polymorphisms in functional dyspepsia

Abstract

Abstract

Functional dyspepsia (FD) is a common gastrointestinal (GI) disorder in the community and in clinical practice. The pathogenesis of FD is largely unknown. However, abnormal gut motility, visceral hypersensitivity, low-grade inflammation and abnormal brain-gut interaction have been incriminated in its pathogenesis. Accumulating evidence, including occurrence of these conditions in family members, suggested that functional gastrointestinal disorders (FGIDs), including FD, might be contributed by genetic factors. The contribution of genetic factors has been extensively studied in various gastrointestinal disorders. FD is a multi-factorial polygenic disorder; however, genetic factors contributing to the development of FD are largely unknown. It remains interesting to explore how the genetic factors influence occurrence of FD. Since gut motility, visceral sensation, and degree of inflammation are all mediated by neuro-peptides, hormones and cytokines and various other proteins, which are transcribed from different genes, alterations in these genes may lead to alterations in these physiological processes. Recent studies showed host genetic factors playing important role in the pathogenesis of FD. Based on the current literature (A PubMed search was done using the key words functional dyspepsia AND gene polymorphisms, functional dyspepsia AND host genetic factors, and functional dyspepsia AND gene pathogenesis), this article reviews the major studies on association between FD and gene polymorphisms [G-protein beta polypeptide-3 (GNB3), Cholecystokinin-A receptor (CCK-AR), interleukin-17F (IL-17F), and interleukin-10 (IL-10); which are extremely important to explain the pathophysiological mechanism of FD].

Key words: Visceral hypersensitivity; gut-motor dysfunction, low-grade inflammation, functional gastrointestinal disorders; gene polymorphisms