title: No association between the common calcium-sensing receptor polymorphism rs1801725 and irritable bowel syndrome.
abstract: BACKGROUND
  The calcium-sensing receptor (CaSR) is a calcium (Ca(2+)) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca(2+)/Mg(2+)- homeostasis and senses interstitial Ca(2+) 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.
  
  
  METHODS
  We have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA.
  
  
  RESULTS
  Genotype frequencies showed no association in the three genotyped case-control samples, neither with IBS nor with IBS subtypes.
  
  
  CONCLUSIONS
  Although we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca(2+) 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.
authors.affiliation: Department of Surgery, Division of Paediatric Surgery, University of Heidelberg, Heidelberg, Germany. Philipp.Romero@med.uni-heidelberg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Romero
authors.affiliation: Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. S.Schmitteckert@med.uni-heidelberg.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schmitteckert
authors.affiliation: TARGID, University Hospital Leuven, Leuven, Belgium. mira.wouters@med.kuleuven.be.
authors.forename: Mira M
authors.initials: MM
authors.lastname: Wouters
authors.affiliation: University of Manchester, Manchester, UK & Mayo Clinic, Jacksonville, USA. Houghton.Lesley@mayo.edu.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Houghton
authors.affiliation: Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. bastian.czogalla@med.uni-heidelberg.de.
authors.forename: Bastian
authors.initials: B
authors.lastname: Czogalla
authors.affiliation: Washington University School of Medicine, St. Louis, USA. gsayuk@dom.wustl.edu.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Sayuk
authors.affiliation: TARGID, University Hospital Leuven, Leuven, Belgium. guy.boeckxstaens@med.kuleiven.be.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.affiliation: Department of Surgery, Division of Paediatric Surgery, University of Heidelberg, Heidelberg, Germany. Patrick.Guenther@med.uni-heidelberg.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Guenther
authors.affiliation: Department of Paediatric Surgery, University of Basel, Basel, Switzerland. Stefan.Holland-Cunz@ukbb.ch.
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
authors.affiliation: Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, 69120, Germany. Beate.Niesler@med.uni-heidelberg.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Niesler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001530:Belgium / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing