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Genetic study of eight AKT1 gene polymorphisms and their interaction with DRD2 gene polymorphisms in tardive

Clement C Zai1, Marco A Romano-Silva, Rudi Hwang

  • 1Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Schizophrenia Research
|October 8, 2008
PubMed

Insights

This study investigated the AKT1 gene

Area of Science:

  • Neuroscience and Genetics
  • Pharmacology and Toxicology

Background:

  • Tardive dyskinesia (TD) is a motor disorder resulting from long-term antipsychotic use.
  • Dopamine D2 receptor blockade by antipsychotics is implicated, affecting downstream signaling pathways.
  • The role of the AKT1 gene in TD pathophysiology remains unexplored.

Purpose of the Study:

  • To investigate the association between AKT1 gene polymorphisms and TD in schizophrenia patients.
  • To explore potential interactions between AKT1 and dopamine D2 receptor (DRD2) gene variants in TD development.

Main Methods:

  • Genotyping of eight AKT1 polymorphisms in a cohort of 193 Caucasian schizophrenia patients (76 with TD).
  • Analysis of individual polymorphisms and haplotypes for association with TD.
  • Statistical analysis to detect gene-gene interactions, specifically between AKT1 and DRD2 variants.

Main Results:

  • No significant association was found between individual AKT1 polymorphisms or haplotypes and TD.
  • A significant interaction (p<1 x 10(-5)) was identified between DRD2 rs6275 and AKT1 rs3730358.
  • This suggests a complex genetic interplay in TD etiology.

Conclusions:

  • The AKT1 gene alone does not appear to be a major risk factor for TD in this schizophrenia cohort.
  • A significant gene-gene interaction between DRD2 and AKT1 may contribute to the development of TD.
  • Further research is warranted to elucidate the functional consequences of this interaction in antipsychotic-induced movement disorders.

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