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. KEY 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 & INFERENCES: 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.
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 IBSpatients and 79 healthy controls. All subjects were Caucasian women of European origin. Irritable bowel syndromepatients filled in a daily diary with five GI symptoms and stool characteristics for 28 days. KEY RESULTS: The TPH1 SNPs showed no association with the diagnosis of IBS. However, among IBSpatients, 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 & INFERENCES: 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: Dimitrios Andreou; Peter Saetre; Thomas Werge; Ole A Andreassen; Ingrid Agartz; Göran C Sedvall; Håkan Hall; Lars Terenius; Erik G Jönsson Journal: Psychiatry Res Date: 2010-05-23 Impact factor: 3.222
Authors: Simon P Dunlop; Nicholas S Coleman; Elaine Blackshaw; Alan C Perkins; Gulzar Singh; Charles A Marsden; Robin C Spiller Journal: Clin Gastroenterol Hepatol Date: 2005-04 Impact factor: 11.382
Authors: Matthew D Coates; Christine R Mahoney; David R Linden; Joanna E Sampson; Jason Chen; Hagen Blaszyk; Michael D Crowell; Keith A Sharkey; Michael D Gershon; Gary M Mawe; Peter L Moses Journal: Gastroenterology Date: 2004-06 Impact factor: 22.682
Authors: P Zill; T C Baghai; P Zwanzger; C Schüle; D Eser; R Rupprecht; H-J Möller; B Bondy; M Ackenheil Journal: Mol Psychiatry Date: 2004-11 Impact factor: 15.992
Authors: Narek Israelyan; Andrew Del Colle; Zhishan Li; Yeji Park; Albert Xing; Jacob P R Jacobsen; Ruth Ann Luna; Dane D Jensen; Moneek Madra; Virginia Saurman; Ray Rahim; Rocco Latorre; Kimberly Law; William Carson; Nigel W Bunnett; Marc G Caron; Kara G Margolis Journal: Gastroenterology Date: 2019-05-07 Impact factor: 22.682
Authors: A Shiotani; H Kusunoki; M Ishii; H Imamura; N Manabe; T Kamada; J Hata; J L Merchant; K Haruma Journal: Neurogastroenterol Motil Date: 2014-11-27 Impact factor: 3.598
Authors: Helmut Grasberger; Lin Chang; Wendy Shih; Angela P Presson; Gregory S Sayuk; Rodney D Newberry; Iordanis Karagiannides; Charalabos Pothoulakis; Emeran Mayer; Juanita L Merchant Journal: Am J Gastroenterol Date: 2013-09-24 Impact factor: 10.864
Authors: Kathleen A Calzone; Jean Jenkins; Alexis D Bakos; Ann K Cashion; Nancy Donaldson; W Gregory Feero; Suzanne Feetham; Patricia A Grady; Ada Sue Hinshaw; Ann R Knebel; Nellie Robinson; Mary E Ropka; Diane Seibert; Kathleen R Stevens; Lois A Tully; Jo Ann Webb Journal: J Nurs Scholarsh Date: 2013-01-31 Impact factor: 3.176