Pharmacogenetics: a laboratory tool for optimizing therapeutic efficiency

TLDR

Pharmacogenetics links an individual’s genotype to drug metabolism, where genetic variants in enzymes such as CYP2D6 can cause poor or ultra‑extensive metabolism, leading to toxicity or therapeutic failure and affecting up to 17 % of patients on commonly prescribed medicines. This review summarizes and updates drug‑metabolizing genotype information, focusing on CYP2D6 genotyping techniques for clinical laboratories to link genetics to therapeutic management. The authors apply genotyping of polymorphic alleles, particularly CYP2D6, to identify individual drug‑metabolism phenotypes. Applying pharmacogenetic knowledge to dosing or drug selection can prevent adverse reactions or therapeutic failure, thereby enhancing therapeutic efficiency.

Abstract

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.