Association between Clozapine-induced Weight Gain and Serotonin 5-HT2C Receptor Gene Polymorphism in Korean Schizophrenic Patients

Weight gain is one of the troublesome adverse reaction to clozapine treatment. This problem can lead to poor adherence to treatment. Clozapine-induced weight gain may be associated with genetic predisposition. Recent studies showed that the polymorphisms of the serotonin 5-HT2C receptor gene is associated with antipsychotic-induced weight gain. This study is to investigate the association of clozapine-induced weight gain with the -759C/T polymorphism of the 5-HT2C receptor gene in Korean schizophrenic patients. The 53 patients were divided into two groups according to the change of body weight between the start and 10 weeks of clozapine treatment. The cutoff level of weight change is 5% increase of initial body weight. Genotypes of the -759C/T polymorphism were identified from Aci I-digested fragments of two-primer products amplified by polymerase chain reaction corresponding to -885 to -634 of the 5-HT2C receptor gene. There were no group differences in basic variables. Four of 32 male and 6 of 21 female patients had the -759T allele, respectively. Clozapine-induced weight gain was significantly less in patients with the -759T allele compared to those without the -759T allele. Weight change tended to be more influenced by the -759T allele in female patients compared to that in male patients, not reaching significance. These findings indicate that the -759C/T polymorphism may be a genetic marker for susceptibility to clozapine-induced weight gain.