Association of GUCY1A3 (rs7692387), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893) gene polymorphism with antiplatelet drug metabolism and prognosis of cardiovascular complications: a systematic review

Introduction: The identification of predictors for resistance to antiplatelet drugs including the search for new gene polymorphisms responsible for the development of the pathological process is an important direction to reduce the risk of complications after cardiac surgery and improve postoperative prognosis. Objective: The study was aimed at investigating the available data on the molecular genetic markers GUCY1A3 (rs7692387), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893) and their association with antiplatelet drug metabolism and adverse outcome after cardiac surgery. Methods: The systematic review was conducted in accordance with the PRISMA criteria. The search was performed in databases Medline (PubMed), Google Scholar and the Russian Science Citation Index using queries and keywords. During the first selection, 3,210 results were obtained. The final analysis included 21 studies conducted between 2004 and 2024. Results: Since 2017 a number of studies have revealed the association of GUCY1A3 gene polymorphism with a high risk of cardiovascular diseases, as well as with an abnormal reaction to acetylsalicylic acid. The mechanism of the pathological process was related to the impact of gene polymorphism on vasoreactivity, platelet aggregation and, as a consequence, on the risk of thrombotic complications. Polymorphisms of CYP2C19*2 and CYP2C19*3 were the most common variants of alleles that reduced clopidogrel metabolism and increased the risk of cardiovascular events. However, therapy based on CYP2C19 genotyping requires a more detailed investigation with the inclusion of ethnic, demographic and socio-economic factors in the analysis. Conclusion: Resistance to acetylsalicylic acid, clopidogrel and other antiplatelet drugs depends on many genetic factors. Further investigation of the GUCY1A3 and CYP2C19 gene polymorphisms is promising for the development of algorithms for genotype-oriented antiplatelet therapy, the introduction of which into medical practice will reduce the number of complications after cardiac surgery and improve the quality of medical care.