CYP2D6 Genotyping in Patients on Psychoactive Drug Therapy

• Published in: Clinical chemistry and laboratory medicine Vol. 38; no. 9; pp. 921 - 927
• Main Authors: TOPIC, Elizabeta, STEFANOVIC, Mario, IVANISEVIC, Ana Maria, BLAZINIC, Franciska, CULAV, Jadranka, SKOCILIC, Zeljko
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Berlin Walter de Gruyter 18.09.2000; New York, NY
• Subjects: Alleles; Amino Acid Substitution; Biological and medical sciences; Catecholaminergic system; Codon, Terminator; Cytochrome P-450 CYP2D6 - genetics; Depressive Disorder - drug therapy; Depressive Disorder - genetics; DNA Primers; Frameshift Mutation; Gene Deletion; Genotype; Humans; Medical sciences; Mutation; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Phenotype; Polymerase Chain Reaction; Psychotropic Drugs - therapeutic use; Schizophrenia - drug therapy; Schizophrenia - genetics; Sequence Deletion; Human; Pharmacogenetics; Neuroleptic; Psychotropic; Toxicity; Cytochrome P450; Schizophrenia; Depression; Genotype; Metabolism; Genetic determinism; Psychosis; Chemotherapy; Phenotype; Treatment; Genetics; Antidepressant agent; Antipsychotic; Mutation; Extrapyramidal syndrome; Polymorphism
• ISSN: 1434-6621; 1437-4331
• 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 CYP2D6*3,*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 2D6*4 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 2D6*4 and 2D6*6, 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 r e s u l t s 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.