gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Article

Send article

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

Meeting Abstract (Hypertonie 2003)

Search Medline for

  • presenting/speaker U.H. Frey - Universitätsklinikum Essen, Else-Kröner-Fresenius-Zentrum für Ernährungsmedizin (Essen, München, D)
  • H. Hauner - Universitätsklinikum Essen, Else-Kröner-Fresenius-Zentrum für Ernährungsmedizin (Essen, München, D)
  • H.S. Bachmann - Universitätsklinikum Essen, Else-Kröner-Fresenius-Zentrum für Ernährungsmedizin (Essen, München, D)
  • M. Meier - Universitätsklinikum Essen, Else-Kröner-Fresenius-Zentrum für Ernährungsmedizin (Essen, München, D)
  • W. Siffert - Universitätsklinikum Essen, Else-Kröner-Fresenius-Zentrum für Ernährungsmedizin (Essen, München, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP34

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch134.shtml

Published: November 11, 2004

© 2004 Frey et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

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.