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

Schizophr Res. 2007 Feb;90(1-3):115-22. doi: 10.1016/j.schres.2006.09.031. Epub 2006 Dec 5.

Abstract

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 < or =3). The DAT expression was studied in fifteen AP-naive patients by [(123)I] 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Basal Ganglia Diseases / chemically induced*
  • Basal Ganglia Diseases / genetics*
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Dose-Response Relationship, Drug
  • Dyskinesia, Drug-Induced / genetics*
  • Female
  • Gene Expression / drug effects
  • Genotype*
  • Humans
  • Male
  • Minisatellite Repeats / genetics*
  • Phenotype*
  • Polymorphism, Genetic / genetics
  • Schizophrenia / drug therapy*
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Antipsychotic Agents
  • Dopamine Plasma Membrane Transport Proteins