Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia

Thomas G. Schulze, Johannes Schumacher, Daniel J. Muller, Harald Krauss, Daniela Alfter, Alexandra Maroldt, Guido Ahle, Ansgar Otto Maroldt, Ana Novo Y Fernandez, Thomas Weber, Tilo Held, Peter Propping, Wolfgang Maier, Markus M. Nothen, Marcella Rietschel

Research output: Contribution to journalArticle

Abstract

Tardive dyskinesia (TD) is a common side effect of long-term medication with typical neuroleptics. TD presents itself by abnormal involuntary movements and may lead to a potentially disabling and chronic clinical course. A vast majority of patients suffering from schizophrenia are smokers. Smoking has been reported to induce the activity of the CYP1A2 enzyme, which is an established metabolic pathway within the disposition of antipsychotics. Recently, a C→A genetic polymorphism in the first intron of the CYP1A2 gene was reported to influence CYP1A2 activity in smokers. Subsequently, a pharmacogenetic study in 85 U.S. patients with schizophrenia (44 smokers, 41 individuals with unknown smoking status) showed the C/C genotype to be associated with higher TD severity (measured by the Abnormal Involuntary Movement Scale, AIMS) than the A/C or A/A genotype. This finding prompted us to investigate whether this effect was also present in a larger German sample of 119 patients with schizophrenia (82 smokers, 37 individuals with unknown smoking status). However, we could not replicate the reported association. The median AIMS scores did not differ between individuals with the A/A, A/C, or C/C genotypes. In an additional analysis, we compared the genotypic and allelic distribution among individuals grouped according to the criteria established by Schooler and Kane [1982: Arch Gen Psychiatry 39:486-487] (persistent TD vs. absent TD). We did not observe a differential genotypic or allelic distribution between the two diagnostic groups. Thus, our results do not support the hypothesis that the C→A polymorphism in the CYP1A2 gene is involved in the etiology of TD in the German population.

Original languageEnglish (US)
Pages (from-to)498-501
Number of pages4
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume105
Issue number6
DOIs
StatePublished - Aug 8 2001
Externally publishedYes

Keywords

  • Abnormal involuntary movements
  • Drug metabolism
  • Genetic association
  • Neuroleptic medication
  • Smoking

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)
  • Genetics

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  • Cite this

    Schulze, T. G., Schumacher, J., Muller, D. J., Krauss, H., Alfter, D., Maroldt, A., Ahle, G., Maroldt, A. O., Fernandez, A. N. Y., Weber, T., Held, T., Propping, P., Maier, W., Nothen, M. M., & Rietschel, M. (2001). Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia. American Journal of Medical Genetics - Neuropsychiatric Genetics, 105(6), 498-501. https://doi.org/10.1002/ajmg.1472