title: Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein beta3 subunit gene (GNB3) C825T polymorphism.
abstract: BACKGROUND
  Sibutramine, a centrally acting noradrenaline and serotonin re-uptake inhibitor, enhances satiety and is frequently used to support weight loss. However, a significant variability exists among individuals concerning the response to sibutramine.
  
  
  METHODS
  We genotyped 111 participants of a randomized placebo-controlled clinical trial for the GNB3 C825T polymorphism and analysed associations of genotypes with treatment outcome. Patients undergoing a structured weight loss programme were treated with either placebo or 15 mg sibutramine daily for 54 weeks.
  
  
  RESULTS
  In the placebo group, the non-pharmacological programme alone resulted in a significantly greater weight loss in individuals with the GNB3 TT/TC genotypes as compared to individuals with the CC genotype (-7.1 +/- 1.2 vs. -2.7 +/- 1.5 kg, P = 0.031). Administration of 15 mg sibutramine was more effective in individuals with the CC genotype than in the subjects with the TT/TC genotypes (weight loss: 7.2 +/- 2.2 vs. 4.1 +/- 2.1 kg, P = 0.0013, sibutramine vs. placebo). In the CC genotype carriers, the odds ratio (OR) for a weight loss greater than 5% (sibutramine vs. placebo) was 6.6 (95% CI 1.8-25.6; P = 0.004) and for a weight loss greater than 10% was 9.6 (95% CI 1.7-53.8; P = 0.010).
  
  
  CONCLUSIONS
  Genotyping for the GNB3 C825T polymorphism is highly predictive for the identification of obese individuals who will benefit from sibutramine treatment.
authors.affiliation: German Diabetes Research Institute, D-40225 Düsseldorf, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.forename: Marion
authors.initials: M
authors.lastname: Meier
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Frey
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001067:Appetite Depressants / Q000627:therapeutic use*; D003503:Cyclobutanes / Q000627:therapeutic use*; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010919:Placebos; D011110:Polymorphism, Genetic
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; D044387:GTP-Binding Protein beta Subunits; D010919:Placebos; C058254:sibutramine