Genes influence effectiveness of weight...(pective. In this randomized double-...),Health

In this randomized, double-blind, pharmacogenetic study, Dr. Camilleri and colleagues evaluated behavioral therapy and sibutramine (10 or 15 mg daily) or placebo for 12 weeks in 181 overweight or obese participants. They measured body weight, BMI, body composition, gastric emptying and genetic variation.

Study results showed that sibutramine at both doses, given in combination with behavioral therapy, caused significant weight loss (p = 0.009). The drug resulted in lower values for weight, BMI and proportion of body fat compared to placebo (p<0.01, p<0.001 and p=0.05, respectively). Weight loss at four weeks was a predictor of weight loss achieved at 12 weeks.

There was a statistically significant gene-by-dose interaction for GNβ3 genotype. This gene determines the function of G proteins, which are involved in translating the message from surface receptors that bind the transmitters serotonin and norepinephrine (e.g. of cells controlling appetite). Those surface receptors are indirectly influenced by sibutramine, which blocks the reuptake of the two transmitters. For each candidate gene, treatment effects were observed at 12 weeks (p<0.017) for all specific genotype variants. The research showed gene pairs (e.g. for GNβ3and α2A-receptor) resulted in greater sibutramine treatment effects on weight (both p<0.002). However, there was no evidence of synergism between combinations of two genotypes on the response to sibutramine therapy compared to the effect on weight loss associated with individual genotypes.

"Our results suggest the genetic make-up of patients could predispose their responsiveness to a drug. This could have important implications for the future of personalized molecular-based or individualized medicine," added Dr. Camilleri. As new and exciting research like this study continues into the causes, prevention and treatments for obesity, the role played by the GI tract is
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