Background: Both, the gene encoding the alpha subunit of G stimulatory proteins (GNAS1) and the Β3 subunit gene (GNB3) of G-proteins are associated with obesity and hypertension. Moreover, the TT/TC825 polymorphism (PM) of GNB3 predicts greater weight loss than the CC825 PM in obese patients (mean BMI about 35kg/m2) undergoing a structured non-pharmacological weight loss programme (SWLP). In contrast, when patients were treated with sibutramine and SLWP, the CC825 PM was associated with greater weight loss than the TT/TC825 PM (Hauner et al., Pharmacogenetics 2003;13:453). Gastric banding (GB) enforces a low calorie diet by diminishing the need for volitional adherence. It is unknown whether these PM predict the variable weight loss seen in patients treated with GB. Methods: 304 severely obese patients (age: 42±1 [mean±SEM] years, f/m: 245/59, BMI: 43.9±0.3 kg/m2) followed prospectively for at least three years after GB were genotyped for the GNB3 C825T, G814A PM and GNAS1 T393T PM. All analyses were performed blinded to the phenotypic characteristics of the study group. Results: Frequency and weight loss are shown in table. Multivariate analysis taking into account potentially confounding parameters such as reoperation rate, use of serotonin reuptake inhibitors, sibutramine or orlistat revealed similar (P>0.7). Blood pressure was not modulated by any PM neither preoperative nor postoperative. Conclusion: No PM studied did predict three-year weight loss nor was associated with high blood pressure in severely obese patients after gastric banding, whereas melanocortin-4 receptor variants (Obes Res 2003,11 Suppl, A24) predict poor outcome after GB. Regardless of the mechanism(s) involved for these discordant findings, GNB3 C825T, G814A and GNAS1 T393C PM`s do not seem to be reliable predictors of long-term weight loss.