TARDIVE-DYSKINESIA AND DEBRISOQUINE 4-HYDROXYLASE (CYP2D6) GENOTYPE IN JAPANESE SCHIZOPHRENICS

Previous studies have shown that many neuroleptics are metabolized by debrisoquine 4-hydrolase (CYP2D6), which exhibits genetic polymorphism s. In Oriental populations, poor metabolizers (PMs) with a lack of CYP 2D6 activity are rare, although the CYP2D610 allele, which is associa ted with decreased CYP2D6 activity, is commonly found. The authors exa mined the relationship between tardive dyskinesia (TD) and CYP2D6 poly morphisms, including the CYP2D610 allele, Subjects consisted of 100 J apanese schizophrenics. TD was evaluated using the Abnormal Involuntar y Movement Scale (AIMS). Genotyping for the presence of the CYP2D63, CYP2D64 and CYP2D6*10 alleles was performed using allele-specific PCR amplification and endonuclease digestions. The frequency of the CYP2D 610 allele was 0.52, and only one allele showed the PM genotype. Ther e was a significant difference in the allelic distribution of CYP2D61 0 between subjects with and without TD. We also found significant geno typic and allelic associations with dichotomized total AIMS scores of 6 or more (moderate or severe abnormal movements) and with scores of l ess than 6 (mild or no movements). After these associations were adjus ted for confounding variables (gender, age, duration of illness and ne uroleptic dose) by regression analysis, the CYP2D610 genotype showed significant association with the total AIMS score, and a modest associ ation with TD occurrence. These results indicate that the CYP2D610 ge notype may play a role in the development of moderate or severe abnorm al movements. (C) 1998 Elsevier Science B.V. All rights reserved.