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 polymorphisms. In Oriental populations, poor metabolizers (PMs) with a lack of CYP2D6 activity are rare, although the CYP2D6*10 allele, which is associated with decreased CYP2D6 activity, is commonly found. The authors examined the relationship between tardive dyskinesia (TD) and CYP2D6 polymorphisms, including the CYP2D6*10 allele. Subjects consisted of 100 Japanese schizophrenics. TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). Genotyping for the presence of the CYP2D6*3, CYP2D6*4 and CYP2D6*10 alleles was performed using allele-specific PCR amplification and endonuclease digestions. The frequency of the CYP2D6*10 allele was 0.52, and only one allele showed the PM genotype. There was a significant difference in the allelic distribution of CYP2D6*10 between subjects with and without TD. We also found significant genotypic and allelic associations with dichotomized total AIMS scores of 6 or more (moderate or severe abnormal movements) and with scores of less than 6 (mild or no movements). After these associations were adjusted for confounding variables (gender, age, duration of illness and neuroleptic dose) by regression analysis, the CYP2D6*10 genotype showed significant association with the total AIMS score, and a modest association with TD occurrence. These results indicate that the CYP2D6*10 genotype may play a role in the development of moderate or severe abnormal movements.
Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
O
O
Ohmori
T
T
Suzuki
H
H
Kojima
T
T
Shinkai
T
T
Terao
T
T
Mita
K
K
Abe
D000483:Alleles; D014150:Antipsychotic Agents / Q000378:metabolism / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6