title: Polymorphisms of 5-HTT LPR and GNβ3 825C>T and Response to Antidepressant Treatment in Functional Dyspepsia: A Study from The Functional Dyspepsia Treatment Trial.
abstract: OBJECTIVE
  The Functional Dyspepsia Treatment Trial reported that amitriptyline (AMI) was associated with adequate relief of functional dyspepsia (FD) symptoms, but the pharmacogenetics of antidepressant response in FD are not known. GNβ3 825C>T CC genotype has been previously linked to FD and TT genotype to antidepressant response in depression. The ss genotype of the 5-HTT LPR variant of the serotonin transporter gene (SLC6A4) has been linked to selective serotonin reuptake inhibitor (SSRI) response. We aimed to examine whether GNβ3 825C>T and 5-HTT LPR polymorphisms result in differential treatment effects in FD patients receiving antidepressant therapy.
  
  
  METHODS
  Participants were randomized to receive placebo, 50 mg AMI, or 10 mg escitalopram (ESC). The primary end point was adequate relief for ≥5 weeks of the last 10 weeks. Genotyping of GNβ3 825C>T and 5-HTT LPR was performed utilizing PCR-based methods.
  
  
  RESULTS
  GNβ3 825C>T and 5-HTT LPR genotype data were available for 256 (88%) and 246 (84%) patients, respectively. Both polymorphisms were in Hardy-Weinberg equilibrium. In tests for differential treatment, neither 5-HTT LPR nor GNβ3 825C>T genotype influenced response to therapy (P=0.89 and P=0.54, respectively). Although there was a tendency for a more favorable response to ESC in the SS/LS genotype compared to the LL genotype groups (40% vs. 31% reporting adequate relief of FD symptoms) among those in the ESC treatment arm, this was not significant (P=0.43).
  
  
  CONCLUSIONS
  GNβ3 825C>T and 5-HTT LPR genetic variants do not alter treatment response to tricyclic and SSRI antidepressants in FD.
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Yuri A
authors.initials: YA
authors.lastname: Saito
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: G Richard
authors.initials: GR
authors.lastname: Locke
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Almazar
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Ernest P
authors.initials: EP
authors.lastname: Bouras
authors.affiliation: Gastroenterology, Northwestern University, Chicago, Illinois, USA.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Howden
authors.affiliation: Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Lacy
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: DiBaise
authors.affiliation: Gastroenterology, St Louis University, St Louis, Missouri, USA.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Prather
authors.affiliation: Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Bincy P
authors.initials: BP
authors.lastname: Abraham
authors.affiliation: Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Hashem B
authors.initials: HB
authors.lastname: El-Serag
authors.affiliation: Gastroenterology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Moayyedi
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Herrick
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Szarka
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.affiliation: Division of Digestive Diseases and Nutrition, NIDDK, Bethesda, Maryland, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Hamilton
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Schleck
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tilkes
authors.affiliation: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.affiliation: Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.|Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Talley
mesh_terms: D000328:Adult; D000639:Amitriptyline / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D015415:Biomarkers; D015283:Citalopram / Q000627:therapeutic use*; D004311:Double-Blind Method; D004415:Dyspepsia / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D015415:Biomarkers; C000595803:GNB3 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D000639:Amitriptyline; D020962:Heterotrimeric GTP-Binding Proteins