Genetic Risk Factors for Adverse Drug Reactions

Abstract

The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs.