G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics.
OBJECTIVE
Clozapine treatment of schizophrenia is effective only in 30-60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia.


METHODS
In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR.


RESULTS
Homozygosity for the T825 allele was more frequent among nonresponders (chi(2) = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (chi(2) = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression.


CONCLUSIONS
Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment.
Kohlrausch
Fabiana B
FB
Universidade Federal do Rio Grande do Sul, Departamento de Genética, Instituto de Biociências, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil.
Salatino-Oliveira
Angélica
A
Gama
Clarissa S
CS
Lobato
Maria Inês
MI
Belmonte-de-Abreu
Paulo
P
Hutz
Mara H
MH
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001938:Brazil; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; C454420:G-protein beta3 subunit; D021122:Protein Subunits; D020962:Heterotrimeric GTP-Binding Proteins; D003024:Clozapine