Modern aspects of pharmacogenetics: from theory to practice in perinatology and pediatrics

Abstract

Pharmacogenetic testing (PT) is a modern tool in the doctor’s practice, which allows to make the right clinical decision in diffi cult cases, when the expected result of medical measures is not achieved. It is clear that certain metabolic processes in thehuman body, as well as a number of diseases, are genetically programmed. Therefore, despite the large number of unexplained mechanisms of individual response to drugs, genetic testing occupies one of the leading positions among methods of selecting drug therapy in complex clinical cases.However, the successful implementation of this promising method must overcome a number of obstacles, including limited evidence of eff ectiveness, ethical, legal, and social factors. The purpose of this review is to highlight modern concepts and practical aspects of the use of PT. The article addresses the problem of expanding the indications for PT when it is not limited to preventive use only. PT allows to identify drugs associated with an increased risk of causing side eff ects, with a narrow therapeutic index, to reduce the number of drugs in treatment, to choose the dosage of the drug. A variety of PT platforms can be used in a physician’s offi ce, which can be broadly divided into two categories–genotyping- based tests and sequencing- based tests. Depending on the gene being tested, diff erent algorithms can be used to generate results. Some gene variants can be described in terms of metabolic activity or general function, while others can only be described as present or absent. Results for gene variants can also be reported as normal, intermediate or low function for the corresponding gene. Pharmacogenetic clinical decision support systems (CDSS) are computer- based systems that assist healthcare providers in prescribing medications at the point of care. These systems provide physicians and other healthcare providers with appropriately fi ltered pharmacogenetic information, such as drug-gene interaction alerts or patient- specifi c treatment recommendations. A pharmacogenetic CDSS can either be integrated into a local hospital information system or used as a stand- alone application such as a web service or mobile application. Pharmacogenetics can increase the quantity and quality of information available to pregnant women and their physicians about medication use during pregnancy. Implementation of PT recommendations into routine pediatric practice requires carefully coordinated strategies at the national, regional, and health system levels. To date, pharmacogenetics provides mosaic information on the association between response to drug therapy and genetic background. It is expected that the next step will be a study in a larger group of participants to investigate the contribution of epigenetic factors and to provide clinical recommendations for adjusting or selecting therapy based on the personal characteristics of the patient.