Artikel
The G(s)alpha gene as a predictor of successful weight loss and cardiovascular side effects with sibutramine
Das G(s)alpha Gen als Prädiktor für erfolgreiche Gewichtsreduktion und kardiovaskuläre Nebenwirkungen unter Therapie mit Sibutramin
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Autoren
Veröffentlicht: | 11. November 2004 |
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Gliederung
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Background
The beta-adrenoceptor G alpha s protein system has been shown to play an important role in the cardiovascular system and lipid mobilization. Sibutramine, a centrally acting noradrenaline and serotonin re-uptake inhibitor is used for adjunct treatment of obesity. However, a significant variability exists among individuals concerning weight loss and cardiovascular side effects.
Methods and Results
We genotyped 89 participants of a randomized placebo-controlled weight loss trial for the common T393C polymorphism in the G alpha s gene and analyzed associations of genotypes with treatment outcome. Patients undergoing a structured weight loss program were additionally treated with either placebo or 15 mg sibutramine daily for 54 weeks. Under placebo treatment, weight loss was significantly different between genotypes (TT -1.6 ± 1.6 kg, TC -5.4 ± 1.4 kg, CC -10.9 ± 2.2 kg; p=0.005). Sibutramine was only effective in T-allele carriers with the strongest effect in TT genotypes (-11.4 ± 3.9 kg versus -1.6 ± 1.6 kg on placebo; p=0.014). No drug effect was observed in CC genotypes (-9.5 ± 2.4 kg versus -10.9 ± 2.2 kg; n.s.). Only T-allele carriers receiving sibutramine had significant increases in resting heart rate and diastolic blood pressure.
Conclusions
Determination of the G alpha s T393C polymorphism not only identifies obese individuals who lose more weight by non-pharmacological treatment but also identifies those who strongly benefit from sibutramine. However, TT genotypes are at higher risk of cardiovascular side effects.