G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics

Pharmacogenomics. 2008 Oct;9(10):1429-36. doi: 10.2217/14622416.9.10.1429.

Abstract

Aims: 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.

Patients & 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Brazil
  • Clozapine / adverse effects
  • Clozapine / therapeutic use*
  • Female
  • Gene Frequency
  • Genotype
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Homozygote
  • Humans
  • Logistic Models
  • Male
  • Polymorphism, Genetic*
  • Protein Subunits / genetics
  • Schizophrenia / drug therapy*
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*
  • White People / genetics

Substances

  • Antipsychotic Agents
  • G-protein beta3 subunit
  • Protein Subunits
  • Heterotrimeric GTP-Binding Proteins
  • Clozapine