Pharmacogenetic study of atypical antipsychotic drug response: involvement of the norepinephrine transporter gene.
The identification of genetic factors underlying individual differences in antipsychotic drug response is of major interest. We investigated the involvement of two norepinephrine transporter gene polymorphisms in response to antipsychotics, comparing patients with strong and weak response to olanzapine and risperidone. We prospectively assessed short-term drug response in 75 Caucasian schizophrenic patients treated with these drugs, using the Positive and Negative Syndrome Scale. We then assessed the association between two SLC6A2 gene polymorphisms and drug response in this sample. No significant difference in genotype distribution was found between responders and non-responders, for the G1287A or T-182C polymorphism. The improvement in PANSS positive subscore was significantly greater in patients homozygous for the A1287 allele than in other patients, and significantly smaller in patients homozygous for the C-182 allele than in other patients. Our results suggest that these polymorphisms are specifically involved in the variation of positive symptoms in schizophrenic patients.
Méary
A
A
AP-HP, Groupe Chenevier-Mondor, Service de Pharmacologie Clinique, Créteil, France. meary@creteil.inserm.fr
Brousse
G
G
Jamain
S
S
Schmitt
A
A
Szöke
A
A
Schürhoff
F
F
Gavaudan
G
G
Lancon
C
C
Macquin-Mavier
I
I
Leboyer
M
M
Llorca
P M
PM
D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001569:Benzodiazepines; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D000077152:Olanzapine; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D018967:Risperidone; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine