Effect of the Common -866G/A Polymorphism of the Uncoupling Protein 2 Gene on Weight Loss and Body Composition under Sib
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ORIGINAL RESEARCH ARTICLE
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Effect of the Common –866G/A Polymorphism of the Uncoupling Protein 2 Gene on Weight Loss and Body Composition under Sibutramine Therapy in an Obese Taiwanese Population Tun-Jen Hsiao,1 Lawrence Shih-Hsin Wu,2,3 Yuchi Hwang,2 Shih-Yi Huang4 and Eugene Lin2 1 2 3 4
College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan Vita Genomics, Inc., Taipei, Taiwan Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan
Abstract
Background: 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. Objective: 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. Methods: 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. Results and Conclusion: 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.
Background Sibutramine is a serotonin and norepinephrine reuptake inhibitor, which is used as an anti-obesity drug to support weight loss in patients with obesity.[1] Weight reduction and changes in body composition with sibutramine treatment in obese patients have been associated with some genetic variants, including the -1291C/G single nucleotide polymorphism (SNP) in the adrenergic alpha-2A-receptor (ADRA2A) gene,[2] the 825C/T (rs5443) SNP in the guanine nucleotide binding protein
beta polypeptide 3 (GNB3) gene,[2-4] and the serotonin transporter gene linked p
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