title: Cytochrome P-450 2D6*10 C188T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients.
abstract: Typical antipsychotic treatment had been postulated to be a risk factor for the susceptibility to tardive dyskinesia (TD). The cytochrome P-450 debrisoquine/sparteine hydroxylase (CYP2D6) metabolizes a majority of antipsychotics and exhibits various phenotypes on enzymatic activities from poor metabolizers to ultrarapid metabolizers. The various phenotypes are encoded by polymorphic genetic variants on the CYP2D6 gene. Although several studies had explored the association between the CYP2D6*10 C188T polymorphism, which encodes the phenotype intermediate metabolizers, and TD in Orientals, the findings were inconclusive. In the present study, we examined the relationship between the CYP2D6*10 C188T polymorphism and the TD occurrence in 216 Chinese schizophrenic patients (113 patients with TD and 103 patients without TD) and explored the correlation between the TD severity assessed by the Abnormal Involuntary Movement Scale (AIMS) and each C188T genotype in the 113 TD patients. Using logistic regression analysis, we found a modest association (p = 0.045) between TD and C188T genotypes. This positive finding was only observed in male patients (p = 0.001), but not in females. Our findings also support the correlation between AIMS scores and C188T polymorphism within the TD group after adjusting for confounding effects with the multiple regression analysis (p = 0.033). We concluded that the CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients.
authors.affiliation: Department of Psychiatry, Yuli Veterans Hospital, Hualien, Taiwan, ROC.
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Wang
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Shun-Chieh
authors.initials: SC
authors.lastname: Yu
authors.forename: Ding-Lieh
authors.initials: DL
authors.lastname: Liao
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Jen-Yeu
authors.initials: JY
authors.lastname: Chen
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lai
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D014150:Antipsychotic Agents / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013912:Threonine / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D012333:RNA, Messenger; D013912:Threonine; D019389:Cytochrome P-450 CYP2D6; D003545:Cysteine