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...
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Published in | Clinical chemistry and laboratory medicine Vol. 38; no. 9; pp. 921 - 927 |
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Main Authors | , , , , , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
Berlin
Walter de Gruyter
18.09.2000
New York, NY |
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Abstract | 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. |
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AbstractList | 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. 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. The polymorphic isoenzyme CYP2D6 has a major role inthe oxidative metabolism of many deal of psychoactivedrugs. Its six mutant alleles (null alleles *3, *4, *5, *6, *7and *8) encode for inactive enzyme molecules. A carrierof two mutant alleles is considered a poor metabolizerphenotype, while a carrier of only one damaged allele isconsidered an intermediate metabolizer phenotype.The aim of the study was to assess the prevalence of nullalleles in a group of psychiatric patients suffering fromdepression (n=49) and schizophrenia (n=86) in comparisonwith healthy individuals (n=145) by the method ofmultiplex allele specific PCR. Only CYP2D6*3,*4 and *6mutant alleles were found in the study subjects. No significantdifference between the depression and controlgroups was found for allele prevalence, genotype orphenotype distribution (p>0.05). However, a significantdifference was observed between schizophrenic patientsand controls for allele frequency (p=0.002), genotypedistribution (p=0.016), and phenotype prevalence(p=0.018). The odds ratio of 2.542 for 2D6*4 suggested asignificant association between this allele and schizophrenia,significantly contributing to poor metabolizerphenotype (odds ratio=5.020). The relationship betweenCYP2D6 gene polymorphism and side effects inschizophrenic patients undergoing long-term psychoactivedrug therapy was investigated. A significantdifference was obtained for allele prevalence (p=0.002),genotype (p=0.029), and phenotype (p=0.002) distributionbetween patients without and with side effects. Arelative risk of 2.626 and 5.333 for 2D6*4 and 2D6*6, respectively, and of 7.08 for poor metabolizer phenotypesuggested a significant association between the hereditarysusceptibility for a particular type of drug metabolism(defect alleles) and side effects. These preliminaryr e s u l t s suggest that the CYP2D6 genotyping appears tobe useful for predicting risks for side effects of psychoactivedrugs in schizophrenic patients, but their usefulnessshould be further explored. 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. Abstract 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. |
Author | Blazinić, Franciska Ivanišević, Ana Maria Topić, Elizabeta Skočilić, Željko Štefanović, Mario Čulav, Jadranka |
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Keywords | 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 |
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References | p_27 Linder M W (p_8) 1997; 43 Topic E (p_13) 1991; 29 p_23 p_24 p_26 Dahl ML (p_25) 1992; 51 Leo RJ (p_10) 1996; 57 p_20 p_21 p_22 Vandel P (p_9) 1995; 59 p_17 p_18 p_1 Henegariu O (p_12) 1997; 23 p_19 p_4 p_6 p_14 p_5 p_15 p_7 Sachse C (p_3) 1997; 60 Kimura S (p_2) 1989; 45 p_11 Gaedikg A (p_16) 1999; 9 |
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Snippet | 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,... Abstract The polymorphic isoenzyme CYP2D6 has a major role in the oxidative metabolism of many deal of psychoactive drugs. Its six mutant alleles (null alleles... The polymorphic isoenzyme CYP2D6 has a major role inthe oxidative metabolism of many deal of psychoactivedrugs. Its six mutant alleles (null alleles *3, *4,... |
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SubjectTerms | 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 |
Title | CYP2D6 Genotyping in Patients on Psychoactive Drug Therapy |
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