Dopamine transporter (DAT) genotype (VNTR) and phenotype in elxtrapyramidal symptoms induced by antipsychotics

Introduction: Impaired dopamine transporter (DAT) function may be involved in antipsychotic (AP)-induced extrapyramidal symptoms (EPS). A polymorphism involving a variable number of tandem repeats (VNTR) has been described in the DAT gene (SLC6A3). Objective: We studied whether the SLC6A3 VNTR polymorphism is a risk or protection factor for AP-induced EPS. We also investigated the relationship between the polymorphism and DAT availability in the schizophrenic patient's brain. Methods: Sixty-one patients receiving AP therapy participated in the EPS study. Of these, thirty-two cases presented EPS (Simpson-Angus > 3) and twenty-nine without EPS (Simpson-Angus <= 3). The DAT expression was studied in fifteen AP-naive patients by [I-123] FP-CIT SPECT. Results: No significant differences were observed for the more common alleles (*9R and *10R) or for genotype frequencies between patients with EPS and those without EPS. The frequency of the *9R and *10R alleles was similar to that described in other European populations. There were no significant differences in striatal DAT binding among the three major VNTR genotype groups. Conclusions: Our results suggest that the VNTR polymorphism did not influence AP-induced EPS and did not affect DAT gene expression or protein function. (c) 2006 Elsevier B.V. All rights reserved.