title: Associations of tryptophan hydroxylase gene polymorphisms with irritable bowel syndrome.
abstract: BACKGROUND
  Alterations in serotonin (5-HT) are suspected in the pathophysiology of irritable bowel syndrome (IBS). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin and has two isoforms: TPH1 and TPH2. Genetic variants in both genes have been studied in various disorders related to serotonin dysregulation. The aim of this study was to examine whether TPH gene variants were associated with IBS and IBS-related gastrointestinal (GI) symptoms.
  
  
  METHODS
  Five single nucleotide polymorphisms (SNPs) from the TPH1 and one SNP from the TPH2 were genotyped in 199 IBS patients and 79 healthy controls. All subjects were Caucasian women of European origin. Irritable bowel syndrome patients filled in a daily diary with five GI symptoms and stool characteristics for 28 days.
  
  
  RESULTS
  The TPH1 SNPs showed no association with the diagnosis of IBS. However, among IBS patients, all five TPH1 SNPs showed some association with diarrhea and loose type of stool consistency, with P-values rating from 0.01 to 0.20. The TPH2 SNP showed a trend towards a reduced risk of IBS and possible associations with stool characteristics, both hard and loose stools. However, no P-values were less than the conservative multiple-comparison-adjusted threshold of 0.001 and hence these results must be interpreted cautiously.
  
  
  CONCLUSIONS
  This study is the first to assess associations of TPH gene variants with IBS-related GI symptoms and stool characteristics. The possible association of TPH gene variants with diarrhea needs to be verified in an independent sample.
authors.affiliation: Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA 98195, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jun
authors.forename: R
authors.initials: R
authors.lastname: Kohen
authors.forename: K C
authors.initials: KC
authors.lastname: Cain
authors.forename: M E
authors.initials: ME
authors.lastname: Jarrett
authors.forename: M M
authors.initials: MM
authors.lastname: Heitkemper
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012701:Serotonin / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D012701:Serotonin; D014365:Tryptophan Hydroxylase