College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan.
Mol Diagn Ther. 2010 Apr 1;14(2):101-6. doi: 10.1007/BF03256359.
Sibutramine, a serotonin and norepinephrine reuptake inhibitor, is used as an anti-obesity drug. Several pharmacogenetic studies have shown correlations between sibutramine effects and genetic variants, such as the 825C/T (rs5443) single nucleotide polymorphism (SNP) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene.
In this study, our goal was to investigate whether a common SNP, -866G/A (rs659366), in the uncoupling protein 2 (UCP2) gene could influence weight reduction and body composition under sibutramine therapy in an obese Taiwanese population.
The study included 131 obese patients, 44 in the placebo group and 87 in the sibutramine group. We assessed the measures of weight loss and body fat reduction at the end of a 12-week treatment period by analysis of covariance (ANCOVA) models using gender, baseline weight, and body fat percentage at baseline as covariates.
By comparing the placebo and sibutramine groups with ANCOVA, our data showed a strong effect of sibutramine on weight loss in the combined UCP2 -866 AA + GA genotype groups (p < 0.001). Similarly, a strong effect of sibutramine on body fat percentage loss was found for individuals with the AA or GA genotypes (p < 0.001). In contrast, sibutramine had no significant effect on weight loss (p = 0.063) or body fat percentage loss (p = 0.194) for individuals with the wild-type GG genotype, compared with the placebo group of the same genotype. Moreover, a potential gene-gene interaction between UCP2 and GNB3 was identified by multiple linear regression models for the weight loss (p < 0.001) and for the percent fat loss (p = 0.031) in response to sibutramine. The results suggest that the UCP2 gene may contribute to weight loss and fat change in response to sibutramine therapy in obese Taiwanese patients.
西布曲明是一种 5-羟色胺和去甲肾上腺素再摄取抑制剂，被用作减肥药。几项遗传药理学研究表明，西布曲明的作用与遗传变异有关，如鸟苷酸结合蛋白β多肽 3（GNB3）基因中的 825C/T（rs5443）单核苷酸多态性（SNP）。
本研究旨在探讨解偶联蛋白 2（UCP2）基因中的常见 SNP-866G/A（rs659366）是否会影响肥胖台湾人群接受西布曲明治疗时的体重减轻和身体成分变化。
该研究纳入了 131 名肥胖患者，其中 44 名接受安慰剂治疗，87 名接受西布曲明治疗。通过协方差分析（ANCOVA）模型，以性别、基线体重和基线体脂百分比为协变量，评估治疗 12 周结束时体重减轻和体脂减少的措施。
通过与安慰剂和西布曲明组的 ANCOVA 比较，我们的数据显示西布曲明对 UCP2-866AA+GA 基因型组合患者的体重减轻有很强的影响（p<0.001）。同样，西布曲明对 AA 或 GA 基因型个体的体脂百分比降低也有很强的影响（p<0.001）。相比之下，西布曲明对同基因型安慰剂组的体重减轻（p=0.063）或体脂百分比降低（p=0.194）没有显著影响。此外，通过多元线性回归模型还发现 UCP2 与 GNB3 之间存在潜在的基因-基因相互作用，可预测西布曲明治疗的体重减轻（p<0.001）和体脂减少（p=0.031）。结果表明，UCP2 基因可能有助于肥胖台湾患者对西布曲明治疗的体重减轻和脂肪变化。
