Topić E, Stefanović M, Ivanisević A M, Blazinić F, Culav J, Skocilić Z
Clinical Institute of Chemistry, School of Medicine, University of Zagreb and Sestre milosrdnice University Hospital, Zagreb, Croatia.
Clin Chem Lab Med. 2000 Sep;38(9):921-7. doi: 10.1515/CCLM.2000.135.
The polymorphic isoenzyme CYP2D6 has a major role in the oxidative metabolism of many deal of psychoactive drugs. Its six mutant alleles (null alleles *3, *4, *5, *6, 7 and 8) encode for inactive enzyme molecules. A carrier of two mutant alleles is considered a poor metabolizer phenotype, while a carrier of only one damaged allele is considered an intermediate metabolizer phenotype. The aim of the study was to assess the prevalence of null alleles in a group of psychiatric patients suffering from depression (n=49) and schizophrenia (n=86) in comparison with healthy individuals (n=145) by the method of multiplex allele specific PCR. Only CYP2D63,4 and 6 mutant alleles were found in the study subjects. No significant difference between the depression and control groups was found for allele prevalence, genotype or phenotype distribution (p>0.05). However, a significant difference was observed between schizophrenic patients and controls for allele frequency (p=0.002), genotype distribution (p=0.016), and phenotype prevalence (p=0.018). The odds ratio of 2.542 for 2D64 suggested a significant association between this allele and schizophrenia, significantly contributing to poor metabolizer phenotype (odds ratio=5.020). The relationship between CYP2D6 gene polymorphism and side effects in schizophrenic patients undergoing long-term psychoactive drug therapy was investigated. A significant difference was obtained for allele prevalence (p=0.002), genotype (p=0.029), and phenotype (p=0.002) distribution between patients without and with side effects. A relative risk of 2.626 and 5.333 for 2D64 and 2D66, respectively, and of 7.08 for poor metabolizer phenotype suggested a significant association between the hereditary susceptibility for a particular type of drug metabolism (defect alleles) and side effects. These preliminary results suggest that the CYP2D6 genotyping appears to be useful for predicting risks for side effects of psychoactive drugs in schizophrenic patients, but their usefulness should be further explored.
多态性同工酶CYP2D6在许多精神活性药物的氧化代谢中起主要作用。其六个突变等位基因（无效等位基因3、4、5、6、7和8）编码无活性的酶分子。携带两个突变等位基因的个体被认为是代谢不良型，而仅携带一个受损等位基因的个体被认为是中间代谢型。本研究的目的是通过多重等位基因特异性PCR方法，评估一组患有抑郁症（n = 49）和精神分裂症（n = 86）的精神病患者与健康个体（n = 145）中无效等位基因的流行情况。在研究对象中仅发现了CYP2D63、4和6突变等位基因。在等位基因流行率、基因型或表型分布方面，抑郁症组与对照组之间未发现显著差异（p>0.05）。然而，在精神分裂症患者与对照组之间，观察到等位基因频率（p = 0.002）、基因型分布（p = 0.016）和表型流行率（p = 0.018）存在显著差异。2D64的优势比为2.542，表明该等位基因与精神分裂症之间存在显著关联，对代谢不良型有显著影响（优势比 = 5.020）。研究了CYP2D6基因多态性与接受长期精神活性药物治疗的精神分裂症患者副作用之间的关系。在无副作用和有副作用的患者之间，等位基因流行率（p = 0.002）、基因型（p = 0.029）和表型（p = 0.002）分布存在显著差异。2D64和2D66的相对风险分别为2.626和5.333，代谢不良型的相对风险为7.08，表明特定类型药物代谢的遗传易感性（缺陷等位基因）与副作用之间存在显著关联。这些初步结果表明，CYP2D6基因分型似乎有助于预测精神分裂症患者精神活性药物副作用的风险，但其有用性仍需进一步探索。
