科研之友
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摘要
Background & Aims: Weight loss in response to sibutramine is highly variable. We assessed the association of specific markers of polymorphisms of candidate alpha 2A adrenoreceptor, S-HT transporter, and GN beta 3 genes and weight loss with sibutramine. Methods: We conducted a randomized, double-blind, pharmacogenetic study of behavioral therapy and sibutramine (10 or 15 mg daily) or placebo for 12 weeks in 181 overweight or obese participants. We measured body weight, body mass index, body composition, gastric emptying, and genetic variation (alpha 2A C1291G, 5-HTTLPR, and GN beta 3 C825T genotypes). Analysis of covariance was used to assess treatment effects on and associations of the specific markers of candidate genes with weight loss and body composition. Result: Sibutramine, 10 and 15 mg, caused weight loss (P = .009); there was a statistically significant gene by dose interaction for GN beta 3 genotype. For each candidate gene, significant treatment effects at 12 weeks were observed (P < .017) for all specific genotype variants (Delta weight loss in the 2 sibutramine doses vs placebo): alpha 2A CC (Delta, similar to 5 kg), GN beta 3 TC/TT (Delta, similar to 6 kg), and 5-HTTLPR LS/SS (Delta, similar to 4.5 kg). Gene pairs resulted in significantly greater sibutramine treatment effects on weight (both P < .002): in participants with 5-HTTLPR LS/SS with GN beta 3 TC/TT; Delta, similar to 6 kg and those with alpha 2A CC with GN beta 3 TC/TT; Delta, similar to 8 kg; however, effects were not synergistic. Treatment with sibutramine also resulted in significantly greater reduction of body fat for specific alpha 2A CC and GN beta 3 TC/TT genotype variants individually (both P < .02). Conclusions: Patient selection based on candidate genes may enhance response to multidimensional sibutramine and behavioral therapy for obesity.
- 出版日期2008-10
