Predictive Biomarkers and Personalized Therapy: Use of Pharmacogenetic Testing in a Scandinavian Perspective

Abstract

Precision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.

Keywords: drug consumption; drug–gene interaction; pharmacogenetics testing; precision medicine; predictive biomarkers.

FIGURE 1

Illustration of phenotype and phenoconversion. Note: Genotype scores for CYP450 metabolic activity are classified into five different phenotypes: ‘poor metabolizer’ (PM), ‘intermediate metabolizer’ (IM), ‘extensive metabolizer’ (EM; normal activity) and ‘rapid or ultra‐rapid metabolizer’ (RM or UM) shown in this fig. as RM. The same considerations also apply to the SLCO1B1 transporter: ‘normal function’ (NF), ‘intermediate function’ (IF) or ‘low function’ (LF) of the transporter. Phenoconversion has been shown to change a person's phenotype, that is, a person only taking Drug A can be phenoconverted when additional taking Drug B.