Kapitany T, Meszaros K, Lenzinger E, Schindler S D, Barnas C, Fuchs K, Sieghart W, Aschauer H N, Kasper S
Department of General Psychiatry, University of Vienna, Austria.
Schizophr Res. 1998 Jul 27;32(2):101-6. doi: 10.1016/s0920-9964(98)00038-3.
In the present study, the occurrence of tardive dyskinesia (TD) in chronic schizophrenia patients was investigated in relation to pharmacogenetic polymorphisms. It is known that the metabolism of important neuroleptic drugs is influenced by polymorphisms of the CYP2D6 gene, which encodes the cytochrome P450 enzyme debrisoquine/spartein hydroxylase. Forty-five patients meeting the DSM IV criteria for schizophrenia, chronic course, were recruited. The patients were examined for the mutations CYP2D63, CYP2D64 and CYP2D6*5. The CYP2D6 genotype distribution in the patient group did not differ from that in healthy Caucasian populations. Tardive dyskinesia was found in 26 patients (57.8%). When comparing patients without CYP2D6 mutations with patients heterozygous for one mutation, we found a higher incidence of TD in the latter (81.3% vs. 46.4%, p = 0.031, multiple regression analysis), which demonstrates a significant influence of the CYP2D6 genotype of the manifestation of TD. As slight differences in the metabolism of drugs in patients heterozygous for CYP2D6 mutations and patients without such mutations are known, we conclude that heterozygous carriers of 2D6 mutated alleles may show an increased susceptibility to developing TD.
在本研究中，我们调查了慢性精神分裂症患者迟发性运动障碍（TD）的发生与药物遗传多态性之间的关系。已知重要抗精神病药物的代谢受CYP2D6基因多态性的影响，该基因编码细胞色素P450酶异喹胍/鹰爪豆碱羟化酶。招募了45名符合精神分裂症DSM-IV标准且病程为慢性的患者。对这些患者进行了CYP2D63、CYP2D64和CYP2D6*5突变检测。患者组的CYP2D6基因型分布与健康白种人群无异。26名患者（57.8%）出现迟发性运动障碍。在比较无CYP2D6突变的患者与有一个突变的杂合子患者时，我们发现后者的TD发生率更高（81.3%对46.4%，p = 0.031，多元回归分析），这表明CYP2D6基因型对TD的表现有显著影响。由于已知CYP2D6突变杂合子患者与无此类突变患者在药物代谢方面存在细微差异，我们得出结论，2D6突变等位基因的杂合子携带者可能对发生TD表现出更高的易感性。
