Elizabeta Topi?, Mario ?tefanovi?, Ana Maria Ivani?evi?, Franciska Blazini?, Jadranka ?ulav, ?eljko Sko?ili?
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
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.
Clinical Chemical Laboratory Medicine, Walter de Gruyter
Print ISSN: 1434-6621
Volume: 38, 09/2000
Pages: 921 - 927
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