Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein beta3 subunit gene (GNB3) C825T polymorphism.
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.
Hauner
Hans
H
German Diabetes Research Institute, D-40225 Düsseldorf, Germany.
Meier
Marion
M
Jöckel
Karl-Heinz
KH
Frey
Ulrich H
UH
Siffert
Winfried
W
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
D001067:Appetite Depressants; D003503:Cyclobutanes; D044387:GTP-Binding Protein beta Subunits; D010919:Placebos; C058254:sibutramine