Hauner Hans, Meier Marion, Jöckel Karl-Heinz, Frey Ulrich H, Siffert Winfried
German Diabetes Research Institute, D-40225 Düsseldorf, Germany.
Pharmacogenetics. 2003 Aug;13(8):453-9. doi: 10.1097/00008571-200308000-00003.
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.
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.
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).
Genotyping for the GNB3 C825T polymorphism is highly predictive for the identification of obese individuals who will benefit from sibutramine treatment.
西布曲明是一种中枢作用的去甲肾上腺素和5-羟色胺再摄取抑制剂，可增强饱腹感，常用于辅助减肥。然而，个体对西布曲明的反应存在显著差异。
我们对一项随机安慰剂对照临床试验的111名参与者进行了GNB3 C825T多态性基因分型，并分析了基因型与治疗结果的关联。接受结构化减肥计划的患者，分别接受安慰剂或每日15毫克西布曲明治疗，为期54周。
在安慰剂组中，与CC基因型个体相比，GNB3 TT/TC基因型个体仅通过非药物计划实现的体重减轻显著更多（-7.1±1.2 vs. -2.7±1.5千克，P = 0.031）。15毫克西布曲明对CC基因型个体的疗效优于TT/TC基因型个体（体重减轻：7.2±2.2 vs. 4.1±2.1千克，P = 0.0013，西布曲明与安慰剂相比）。在CC基因型携带者中，体重减轻超过5%（西布曲明与安慰剂相比）的优势比（OR）为6.6（95%CI 1.8 - 25.6；P = 0.004），体重减轻超过10%的优势比为9.6（95%CI 1.7 - 53.8；P = 0.010）。
GNB3 C825T多态性基因分型对于识别将从西布曲明治疗中获益的肥胖个体具有高度预测性。
