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

Tardive dyskinesia (TD) is a common side effect of long-term medication wit h typical neuroleptics. TD presents itself by abnormal involuntary movement s and may lead to a potentially disabling and chronic clinical course. A va st majority of patients suffering from schizophrenia are smokers. Smoking h as been reported to induce the activity of the CYP1A2 enzyme, which is an e stablished metabolic pathway within the disposition of antipsychotics. Rece ntly, a C-A genetic polymorphism in the first intron of the CYP1A2 gene was reported to influence CYP1A2 activity in smokers. Subsequently, a pharmaco genetic study in 85 U.S. patients with schizophrenia (44 smokers, 41 indivi duals with unknown smoking status) showed the C/C genotype to be associated with higher TD severity (measured by the Abnormal Involuntary Movement Sca le, AIMS) than the A/C or A/A genotype. This finding prompted us to investi gate whether this effect was also present in a larger German sample of 119 patients with schizophrenia (82 smokers, 37 individuals with unknown smokin g status). However, we could not replicate the reported association. The me dian AIMS scores did not differ between individuals with the AIA, A/C, or C /C genotypes. In an additional analysis, we compared the genotypic and alle lic distribution among individuals grouped according to the criteria establ ished by Schooler and Kane [1982: Arch Gen Psychiatry 39:486-487] (persiste nt TD vs. absent TD). We did not observe a differential genotypic or alleli c distribution between the two diagnostic groups. Thus, our results do not support the hypothesis that the C-->A polymorphism in the CYP1A2 gene is in volved in the etiology of TD in the German population. (C) 2001 Wiley-Liss, Inc.