engleski

Genetic polymorphism of CYP450

The genetic polymorphism of cytochrome P450 (CYP) monooxigenase CYP2D6, CYP2C19, CYP2E1 and CYP2C9 with many allelic variants causes defective, quantitatively altered, reduced or enhanced rates of drug metabolism. In view of these phenomena, individual differences can be recognized in the way people react to drugs. Significant differences in serum drug concentrations even when patients are treated with the same dosage can be observed, thereby affecting the side effects and the therapeutic effect itself. 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 relationship between CYP2D6 gene polymorphism and side effects in schizophrenic patients undergoing long term psychoactive drug therapy was investigated in a group of 135 patients by multiplex PCR. A significant difference was obtained for allele prevalence (p=0.002), genotype (p=0.029), and predicted 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 investigated.

cytochrome P450; polymorphisms

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