C825T polymorphism in the human G protein beta3 subunit gene is associated with long-term clozapine treatment-induced body weight change in the Chinese population.

Weight gain, leading to further morbidity and poor treatment compliance, is a common adverse effect of treatment with clozapine. The C825T polymorphism in the human G protein beta3 subunit gene has been noted to be associated with obesity, hypertension and coronary artery disease. Clozapine increases the level of G protein beta3 subunit in the rat striatum. The aim of the present study was to investigate the relationship between G protein beta3 polymorphisms and clozapine-induced body weight change in a Chinese population during long-term treatment. One hundred and thirty-four schizophrenic patients, who were treated with clozapine continuously (13.4+/-0.5 months), were genotyped for G protein beta3 subunit C825T polymorphism. None of these patients received second-generation antipsychotics before clozapine treatment. Body weight was monitored at baseline before clozapine treatment and at the endpoint after clozapine treatment. Patients with the TT type experienced significantly more weight gain (16.2+/-2.5%) compared to those with CT (9.3+/-1.2%) or CC types (5.5+/-2.4%) after long-term clozapine treatment (P = 0.003). Further stratification by gender demonstrated that the effect of C825T polymorphism on weight gain remained significant both in males and females. These findings confirm the importance of genetic factors in body weight change induced by long-term clozapine treatment in patients with schizophrenia, and indicate a role for the G protein beta3 subunit in body weight regulation during long-term clozapine treatment.