Abstract
Aim:
To investigate the possible association of the CYP2D6 gene C100T polymorphism and the CYP1A2 gene C163A polymorphism with tardive dyskinesia (TD) in Chinese patients with schizophrenia.
Methods:
The recruited schizophrenic patients were assessed with the Abnormal Involuntary Movement Scale (AIMS), and divided into groups with TD (n=91) and without TD (n=91) according to the AIMS score. Polymorphisms of the CYP2D6 and CYP1A2 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP).
Results:
No allele frequencies deviated from Hardy-Weinberg equilibrium. No significant differences in genotypes frequencies of the CYP2D6 C100T polymorphism were observed between patients with TD and without TD (χ2=4.078, P>0.05), but patients with TD had a significant excess of the T allele compared with those without TD (χ2=4.28, P<0.05). Moreover, the frequency of the CYP1A2 C allele in patients with TD was significantly higher than that in those without TD (χ2=6.38, P<0.05). An association between TD and the CYP2D6 100T and CYP1A2 163C alleles was observed. Additionally, there were no differences in the mean AIMS scores among different genotypes in TD patients as a group or in smokers. The results of logistic regression analysis demonstrated that mean age and duration of illness were risk factors for TD, but not sex, cumulative exposure to neuroleptic drugs in years, CYP2D6 or CYP1A2 genotype.
Conclusion:
The C100T polymorphism of the CYP2D6 gene and the C163A polymorphism of the CYP1A2 gene may be associated with neuroleptic drug-induced tardive dyskinesia in Chinese patients with schizophrenia. However, genetic factors have a weaker association with susceptibility to TD compared with mean age and duration of illness.
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References
Christensen AV, Nielsen IM . Dopaminergic supersensitivity: influence of dopamine agonists, cholinergics, anticholinergics, and drugs used for the treatment of tardive dyskinesia. Psychophar-macology (Berl) 1979; 62: 111–6.
Gasey DE . Tardive dyskinesia: pathophysiology and animal models. J Clin Psychiatry 2000; 61 Suppl 4: 5–9.
Dalgalarrondo P, Gattaz WF . Basal ganglia abnormalities in tardive dyskinesia. Possible relationship with duration of neuroleptic treatment. Eur Arch Psychiatry Clin Neurosci 1994; 244: 272–7.
Brosen K . Drug-metabolizing enzymes and therapeutic drug monitoring in psychiatry. Ther Drug Monit 1996; 18: 393–6.
Basile VS, Ozdemir V, Masellis M . A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry 2000; 5: 410–7.
Meyer UA . Pharmacogenetics: the slow, the rapid, and the ultrarapid. Proc Natl Acad Sci USA 1994; 91: 1983–4.
Ball SE, Scatina J, Kao J . Population distribution and effects on drug metabolism of a genetic variant in the 5′ promoter region of CYP3A4. Clin Pharmacol Ther 1999; 66: 288–94.
Garcia-Barcelo M, Chow LY, Chiu HF . Genetic analysis of the CYP2D6 locus in a Hong Kong Chinese population. Clin Chem 2000; 46: 18–23.
Hamdy SI, Hiratsuka M, Narahara K . Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population. Br J Clin Pharmacol 2003; 55: 321–4.
Wang SL, Huang JD, Lai MD, Liu BH, Lai ML . Molecular basis of genetic variation in debrisoquine hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 1993; 53: 410–5.
Liou YJ, Wang YC, Bai YM . Cytochrome P-450 2D6*10 C100T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients. Neuro-psychobiology 2004; 49: 167–73.
Lohmann PL, Bagli M, Krauss H . CYP2D6 polymorphism and tardive dyskinesia in schizophrenic patients. Pharmacopsychiatry 2003; 36: 73–8.
Schulze TG, Schumacher J, Muller DJ, Krauss H, Alfter D, Maroldt A . Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia. Am J Med Genet 2001; 105: 498–501.
Tiwari AK, Deshpande SN, Rao AR, Bhatia T, Lerer B, Nimgaonkar VL . Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: III. Lack of association of CYP3A4 and CYP2D6 gene polymorphisms. Schizophr Res 2005; 75: 21–6.
Schooler NR, Kane JM . Research diagnosis of tardive dyskinesia. Arch Gen Psychiatry 1982; 39: 486–7.
Garcia-Barcelo M, Chow LY, Chiu HF, Wing YK, Lee DT, Lam KL, et al. Genetic analysis of the CYP2D6 locus in a HongKong Chinese population. Clin Chem 2000; 46: 18–23.
Matsumoto C, Ohmori O, Shinki T . Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia. Psychiatr Genet 2004; 14: 209–13.
Ohmori O, Suzuki T, Kojima H . Tardive dyskinesia and debrisoquine 4–hydroxylase (CYP2D6) genotype in Japanese schizophrenics. Schizophr Res 1998; 32: 102–13.
Sachse C, Brockmoller J, Bauer S . Functional significance of CjuA polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999; 47: 445–9.
Kalow W, Tang BK . Caffeine as ametabolic probe: exploration of the enzyme-induced effect of cigarette smoking. Clin Pharmacol Ther 1991; 49: 44–8.
Kirch DG, Alho AM, Wyatt RJ . Hypothesis: a nicotine-dopamine interaction linking smoking with Parkinson's disease and tardive dyskinesia. Cell Mol Neurobiol 1988; 8: 285–91.
Nakajima M, Yokoi T, Mizutani M . Genetic polymorphism in the 5-flanking region of the CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem 1999; 125: 803–8.
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Fu, Y., Fan, Ch., Deng, Hh. et al. Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dyskinesia in Chinese schizophrenic patients. Acta Pharmacol Sin 27, 328–332 (2006). https://doi.org/10.1111/j.1745-7254.2006.00279.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00279.x
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