Incidence of β3-adrenergic receptor polymorphism and prediction of successful weight reduction with mazindol therapy in severely obese Japanese subjects.

Mazindol, a centrally acting monoamine re-uptake inhibitor, enhances satiety and supports body weight loss, but response to this drug among obese patients is very variable. The possible involvement of the Trp64Arg polymorphism of the β3-adrenergic receptor (ADRB3) gene in the development of severe obesity and weight loss response to anorexigenic drugs has not been established. In the present study, the allelic frequency of the Trp64Arg ADRB3 gene polymorphism was determined in massively obese Japanese outpatients (BMI>35kg/m2), and we investigated whether allelic differences may determine the weight loss effect of mazindol. The allelic frequency of Trp64Arg heterozygotes and homozygotes did not differ in severely obese subjects compared to non-obese subjects. Trp64Arg heterozygotes experienced significantly increased weight loss and reduced blood pressure following mazindol administration for 12 weeks. Thus the ADRB3 gene polymorphism is predictive for difficulty in weight reduction with mazindol treatment, but is not related to the development of severe obesity in the Japanese population.