Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency.

TLDR

Pharmacogenetics links an individual’s genotype to drug metabolism, where genetic polymorphisms in enzymes such as CYP2D6 can cause poor or ultra‑rapid metabolism, leading to toxicity or therapeutic failure, and genotyping can guide dosing to improve safety and efficacy. The review aims to summarize and update information on drug‑metabolizing genotypes, focusing on CYP2D6 genotyping techniques that can be applied by clinical laboratories to link human genetics to therapeutic management. The review compiles current CYP2D6 genotyping methods that clinical laboratories can use to associate genetic variants with drug metabolism.

Abstract

Pharmacogenetics is the study of the linkage between an individual's genotype and that individual's ability to metabolize a foreign compound. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Phenotypes exhibiting poor and ultraextensive metabolism result from genetic variance (polymorphism) of enzymes involved in metabolism. Thus, in pharmacogenetic studies one applies genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug metabolism phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic efficiency. More than 25 commonly prescribed medicines are metabolized by the cytochrome P-4502D6 (CYP2D6) isoenzyme, and polymorphism of the CYP2D6 gene affects the therapeutic management of up to 17% of individuals in some ethnic groups. In this review, we summarize and update information concerning drug-metabolizing genotypes with emphasis on CYP2D6 genotyping techniques that can be applied by the clinical laboratory for linking human genetics to therapeutic management.