Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics.
BACKGROUND
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.
Lafuente
Amalia
A
Dep. Farmacología y Química Terapéutica, Universidad de Barcelona, IDIBAPS, Casanova 143, E-08036 Barcelona, Spain. amalialafuente@ub.edu
Bernardo
Miquel
M
Mas
Sergi
S
Crescenti
Anna
A
Aparici
Monica
M
Gassó
Patricia
P
Catalan
Rosa
R
Mateos
Jose J
JJ
Lomeña
Francisco
F
Parellada
Eduard
E
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy*; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D050483:Dopamine Plasma Membrane Transport Proteins