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Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia

Matsumoto, Chimaa; Ohmori, Osamua b; Shinkai, Takahiroa; Hori, Hirokoa; Nakamura, Juna

Original Articles

Objective: Recent studies have revealed positive associations between tardive dyskinesia (TD) and genetic polymorphisms of several cytochrome P450 (CYP) subfamilies that are involved in pharmacokinetic process of antipsychotic drugs. In the present study, we analyzed the relationship between TD and two polymorphisms of the CYP1A2 gene, 734C/A and −2964G/A, in a sample of Japanese patients with schizophrenia.

Methods: We studied 199 Japanese patients with schizophrenia. We used the Abnormal Involuntary Movement Scale to evaluate TD. Two polymorphisms of the CYP1A2 gene, 734C/A and −2964 G/A were genotyped by means of polymerase chain reaction and restriction fragment length polymorphism analysis.

Results: Neither the 734C/A nor the −2964G/A polymorphism was associated with TD [734C/A genotype: χ2=0.02, degrees of freedom (df)=2, P=1.00; allele: χ2=0.02, df=1, P=0.89; −2964G/A genotype: χ2=0.21, df=2, P=0.90; allele: χ2=0.15, df=1, P=0.70]. In addition, CYP1A2 haplotype was associated with TD (χ2=0.24, df=3, P=0.97). Furthermore, in both the subgroup of smokers and the subgroup of patients receiving high-dosage antipsychotics (chlorpromazine equivalent >1000 mg), neither the 734C/A nor the −2964G/A polymorphism was associated with TD.

Conclusions: We did not find significant associations between the 734C/A and −2964G/A polymorphisms of CYP1A2 gene and TD in Japanese patients with schizophrenia. Our results suggest that these CYP1A2 gene polymorphisms may not contribute to TD susceptibility.

aDepartment of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan

bWakato Hospital, Wakamatsu-ku, Kitakyushu, Japan

Sponsorship: This work was supported in part by a Grant-in-Aid for Young Scientists B, number 13770565, for Science Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan and a scholarship from the Japanese Society of Clinical Neuropsychopharmacology (TS).

Correspondence and requests for reprints to Chima Matsumoto, M.D., Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, 807-8555, Japan

Tel: +81 93 691 7253; fax: +81 93 692 4894;

e-mail: chima-sgy@umin.ac.jp

Received July 7 2003 Accepted January 26 2004

© 2004 Lippincott Williams & Wilkins, Inc.