Interactive effect of cytochrome P450 17alpha-hydroxylase and dopamine D3 receptor gene polymorphisms on abnormal involuntary movements in chronic schizophrenia

Biol Psychiatry. 2002 Feb 1;51(3):261-3. doi: 10.1016/s0006-3223(01)01302-6.

Abstract

Background: Tardive dyskinesia is a chronic adverse effect of anti psychotic drugs, where association with a polymorphic site in the dopamine D3 receptor gene has been previously reported. Cytochrome P 450 17alpha-hydroxylase activity has been implicated with modulation of central dopamine release as well as neuroprotection. We investigated the association of a T -->C variation in the cytochrome P 450 17alpha-hydroxylase gene with tardive dyskinesia in patients with chronic schizophrenia.

Methods: Cytochrome P 450 17 allele and genotype frequencies were compared between matched schizophrenia patients with (n = 55) or without tardive dyskinesia (n = 58). Interactive effects of cytochrome P 450 17alpha-hydroxylase with the dopamine D3 Ser9Gly polymorphism on abnormal involuntary movements were examined.

Results: There was no difference in cytochrome P 450 17alpha-hydroxylase genotype distribution between patients with and without tardive dyskinesia; however, patients carrying the cytochrome P 450 17alpha-hydroxylase A2-A2 genotype and the dopamine D3gly allele had the highest orofacial (p <.04), distal (p <.05), and incapacitation (p <.04) scores on the Abnormal Involuntary Movements Scale.

Conclusions: Schizophrenia patients who carry the dopamine D3gly allele and the cytochrome P 450 17alpha-hydroxylase A2-A2 genotype may be more likely to develop abnormal orofoacial and distal involuntary movements and to be incapacitated by these movements when chronically exposed to classical antipsychotic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / adverse effects
  • Chronic Disease
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dyskinesia, Drug-Induced / diagnosis
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3
  • Receptors, Glycine / genetics
  • Receptors, Glycine / metabolism
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism*
  • Severity of Illness Index
  • Steroid 17-alpha-Hydroxylase / genetics*
  • Steroid 17-alpha-Hydroxylase / metabolism*

Substances

  • Antipsychotic Agents
  • DRD3 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Glycine
  • Cytochrome P-450 Enzyme System
  • Steroid 17-alpha-Hydroxylase