CYP2D6 genotyping in patients on psychoactive drug therapy.
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 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.
Topić
E
E
Clinical Institute of Chemistry, School of Medicine, University of Zagreb and Sestre milosrdnice University Hospital, Zagreb, Croatia. elizabeta.topic@zg.tel.hr
Stefanović
M
M
Ivanisević
A M
AM
Blazinić
F
F
Culav
J
J
Skocilić
Z
Z
D000483:Alleles; D019943:Amino Acid Substitution; D018388:Codon, Terminator; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017931:DNA Primers; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D016368:Frameshift Mutation; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D017384:Sequence Deletion
D018388:Codon, Terminator; D017931:DNA Primers; D011619:Psychotropic Drugs; D019389:Cytochrome P-450 CYP2D6