Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia

Psychiatry Res. 2004 Jun 30;127(1-2):1-7. doi: 10.1016/j.psychres.2004.03.011.

Abstract

Several lines of evidence suggest that tardive dyskinesia (TD) may be associated with altered dopaminergic neurotransmission. We hypothesized that deranged dopamine degradation enzyme activities might be related to the susceptibility to TD through altered dopaminergic neurotransmission in the central nervous system. In the present study, we investigated the relationship between the gene polymorphisms of three dopamine degradation enzymes and TD. We genotyped the valine/methionine polymorphism of codon 108/158 in the catechol-O-methyltransferase (COMT) gene, the 30-bp repeat polymorphism in the promoter of the monoamine oxidase A (MAOA) gene, and the A/G polymorphism in intron 13 of the monoamine oxidase B (MAOB) gene in 206 Japanese patients with schizophrenia. No significant difference was found in total scores on the Abnormal Involuntary Movement Scale (AIMS) among the subject groups, sorted according to the COMT, MAOA and MAOB genotypes. Moreover, no significant difference was found in allele frequencies between patients with TD and patients without TD for any of the polymorphisms. As both COMT and MAO genes are involved in degrading catecholamines, we also sought evidence for additive and epistatic effects, but none was observed. Our data, therefore, do not support the hypothesis that polymorphisms in COMT, MAOA, and MAOB genes are involved individually or in combination in the predisposition to TD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Catechol O-Methyltransferase / genetics*
  • Codon / genetics
  • DNA Primers / genetics
  • Dopamine / genetics*
  • Dyskinesia, Drug-Induced / etiology*
  • Dyskinesia, Drug-Induced / genetics*
  • Female
  • Gene Expression / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haloperidol / adverse effects*
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Monoamine Oxidase / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • RNA Stability
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics*
  • Synaptic Transmission / physiology

Substances

  • Antipsychotic Agents
  • Codon
  • DNA Primers
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Haloperidol
  • Dopamine