Abstract

BackgroundThe calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca2+/Mg2+- homeostasis and senses interstitial Ca2+ levels and thereby controls downstream signalling cascades. Due to its expression in the gut epithelium, the enteric nervous system and smooth muscles and its key function in regulation and coordination of muscular contraction and secretion, it represents an excellent candidate gene to be investigated in the pathophysiology of irritable bowel syndrome (IBS). Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and consequently contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity.MethodsWe have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA.ResultsGenotype frequencies showed no association in the three genotyped case–control samples, neither with IBS nor with IBS subtypes.ConclusionsAlthough we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca2+ levels and disturbed secretion and gut motility which were unfortunately not assessed in the patients genotyped. This underlines the necessity of a more detailed phenotyping of IBS patients and control individuals in future studies.

Highlights

  • The calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes

  • A986S) of the CASR gene, which has not been examined in irritable bowel syndrome (IBS) previously

  • Genotype frequencies did not deviate from Hardy-Weinberg equilibrium and showed no association in the three genotyped case–control samples, neither with IBS nor with IBS subtypes (Table 2)

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Summary

Introduction

The calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes It regulates Ca2+/Mg2+- homeostasis and senses interstitial Ca2+ levels and thereby controls downstream signalling cascades. Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity. A dysfunctional CaSR causing disturbed intestinal Ca2+ absorption may have effects on intestinal motility, secretion [7, 8], neuromuscular excitability, colonic fluid transport, peptide release and contribute to the symptoms seen in functional GI disorders, such as Irritable Bowel Syndrome (IBS). Dysfunction within the ENS [22] and/or central nervous system, along with impaired mucosal barrier function have all been implicated in its pathophysiology [23]

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