title: Diplotypes of the human serotonin 1B receptor promoter predict growth hormone responses to sumatriptan in abstinent alcohol-dependent men.
abstract: BACKGROUND
  Some studies have associated alcohol dependence (AD) with the human serotonin (5-HT)(1B) receptor (HTR1B). This investigation explored the functional responsivity of HTR1B in abstinent AD men using a sumatriptan challenge, while measuring genetic heterogeneity in the HTR1B promoter.
  
  
  METHODS
  Abstinent AD men (n = 27) and abstinent men without any alcohol use disorder (n = 19) were administered 6 mg of sumatriptan succinate, subcutaneously. Plasma samples collected over the following 2 hours were assayed for growth hormone (GH) concentrations. His DNA was genotyped for the A-161T and T-261G polymorphisms of the HTR1B promoter and diplotypes determined.
  
  
  RESULTS
  Integrated GH responses were predicted by interactions of AD and promoter diplotypes, as well as subject ethnicity. The final model accounted for nearly 35% of the variance in GH responses. Post hoc evaluation revealed that AD was associated with a blunting of GH secretion only among individuals with the most common HTR1B diplotype (TT/TT).
  
  
  CONCLUSIONS
  A blunting of GH responses in abstinent AD men was observed only among those with the most common HTR1B promoter diplotype. Less common promoter diplotypes appeared protective. Controlling for genetic background is a useful augmentation of case-control pharmacological challenge strategies designed to elucidate the psychobiology of AD and other complex disorders.
authors.affiliation: Center for the Studies of Addiction, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. mossh@mail.nih.gov
authors.forename: Howard B
authors.initials: HB
authors.lastname: Moss
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hardie
authors.forename: John P
authors.initials: JP
authors.lastname: Dahl
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D016009:Chi-Square Distribution; D005006:Ethnicity; D005838:Genotype; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D011863:Radioimmunoassay; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D018170:Sumatriptan / Q000008:administration & dosage
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D018170:Sumatriptan; D013006:Growth Hormone