CYP2D6 genotyping in patients on psychoactive drug therapy (CROSBI ID 91523)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Topić, Elizabeta ; Štefanović, Mario ; Ivanišević, Ana-Maria ; Blazinić, Franciska ; Čulav, Jadranka ; Skočilić, Željko
engleski
CYP2D6 genotyping in patients on psychoactive drug therapy
The polymorphic isoenzyme CYP2D6 has a major role in the oxidative metabolism of a great 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 (PM) phenotype, while a carrier of only one damaged allele is considered an intermediate metabolizer (IM) 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 all study subjects. No significant difference between depression and control group 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 PM 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 PM phenotype suggested a significant association between the hereditary susceptibility for a particular type of drug metabolism (defect alleles) and side effects. The CYP2D6 phenotyping and genotyping appear to be useful in predicting the effect of psychoactive drugs, but their usefulness in predicting clinical effects should be further explored.
antipsychotic drugs ; multiplex PCR ; CYP2D6 ; schizophrenia ; side effects
Glavni autor: Ivan Brnardić
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Podaci o izdanju
38 (9)
2000.
921-927
objavljeno
1434-6621
1437-4331
10.1515/CCLM.2000.135
Povezanost rada
Temeljne medicinske znanosti