Effects Of DRD2 C957T, C939T Polymorphisms On Response To Clozapine In Schizophrenic Patients

Aims:Dopamine D2 receptor (DRD2) has close association with schizophrenia and acts as an important target for antipsychotics.This study aimed to confirm whether the DRD2 C957T, C939T polymorphisms had effects on response to clozapine in schizophrenic patients.Methods:DRD2 genotype was determined by pyrosequencing for 182 patients with schizophrenia. Fifty-four patients with certain DRD2 genotype were selected to measure the psychotolytic effect of clozapine. They were administered orally clozapine 300 mg/day for 8 weeks, and the steady-state trough concentration of clozapine was measured by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC-MS/MS).Clinical symptoms were evaluated by Positive and Negative Syndrome Scale (PANSS),and the responder was defined as a reduction of≥50% on total PANSS score from baseline.Results:The frequencies of C/C and C/T genotype for C957T in patients were 91.2% and 8.8%, respectively, and 957T allele was 4.4%; the frequencies of C/C,C/T and T/T genotype for C939T in patients were 30.2%,42.3% and 27.5%,respectively, and 939T allele was 48.6%. Compared to patients with C/T genotype,the 957 C/C carriers had greater improvement on the total PANSS score (C/C 17.4±5.3, C/T 13.9±4.7, P=0.030) and positive symptom score (C/C 12.2±3.6,C/T 9.5±3.7, P=0.022).Moreover, the percentage of responder to clozapine in C/C genotype was higher than C/T genotype (C/C:Responder 70.0%, Non-responder 30.0%;C/T:Responder 35.7%, Non-responder 64.3%, P=0.024).It was only found the positive symptom score change in 939 T/T patients was greater than the other two genotypes (C/C 10.5±3.4, C/T 10.6±3.3,T/T 13.7±4.1,P=0.020),and there were no significant differences in total PANSS score or the percentage of responder to clozapine.Conclusions:DRD2 C957T polymorphism was associated with response to clozapine in schizophrenic patients. Compared to C/T genotype, patients with C/C genotype had better response to clozapine, and especially had greater improvement in positive symptom.DRD2 C939T polymorphism was not significantly associated with response to clozapine in schizophrenic patients.