CYP2D6 genotyping in patients on psychoactive drug therapy

The polymorphic isoenzyme CYP2D6 has a major role in the oxidative metaboli sm of many deal of psychoactive drugs. Its six mutant alleles (null alleles *3, *4, *5, *6, *7 and *6) 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 metabolize r phenotype. The aim of the study was to assess the prevalence of null alle les 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, genotyp e 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=0.0 18). The odds ratio of 2.542 for 2D6*4 suggested a significant association between this allele and schizophrenia, significantly contributing to poor m etabolizer phenotype (odds ratio=5.020). The relationship between CYP2D6 ge ne polymorphism and side effects in schizophrenic patients undergoing long- term psychoactive drug therapy was investigated. A significant difference w as obtained for allele prevalence (p=0.002), genotype (p=0.029), and phenot ype (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 o f 7.08 for poor metabolizer phenotype suggested a significant association b etween the hereditary susceptibility for a particular type of drug metaboli sm (defect alleles) and side effects. These preliminary results suggest tha t the CYP2D6 genotyping appears to be useful for predicting risks for side effects of psychoactive drugs in schizophrenic patients, but their usefulne ss should be further explored.