engleski

Pharmacogenetics and clinical laboratory

Pharmacogenetics is a novel branch of pharmacological sciences studying the relationship between genetic predisposition of an individual and his ability to metabolize a drug. Differences in drug metabolism can lead to severe toxicity or therapeutic failure due to changed ratio between the drug dose and concentration of pharmacologically active substance in the blood, and result in genetic modifications, i.e. polymorphism of enzymes included in drug metabolism. Genetic polymorphism based on drug metabolism ability is associated with three phenotype classes. The phenotype of extensive drug metabolizer (EM) is characteristic of normal population. Poor metabolizer (PM) is associated with the accumulation of specific drug substrates in the body, inherited as a recessive autosomal trait due to mutation and/or deletion of both alleles responsible for phenotypic expression. Ultraextensive metabolizer (UEM) is characterized by enhanced drug metabolism due to gene amplification, inherited as an autosomal dominant trait. The methods of molecular biochemistry developed in clinical laboratories are new diagnostic tool that allow detection of allele mutations and recognition of homozygous and heterozygous carriers of mutant genes. The advantage of molecular diagnosis in the field of pharmacogenetics lies in the fact that the results of pharmacogenetic analysis provide data on the genotypic/phenotypic features of an individual concerning his drug metabolizing ability before therapy introduction, thus allowing dose optimization. In addition to the recognition of PM and UEM phenotypes, it also enables a parallel drug metabolized by another enzyme to be used, thus preventing undesired side effects or therapeutic errors due to too low or too high drug doses.

pharmacogenetics; genetic polymorphism; genotyping; cytochrome P450; CYP2D6

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