Novel Genetic Variants Associated With Cardiovascular Events in Clopidogrel and Aspirin Users

Abstract

Despite reports showing the effects of genetic variations on major adverse cardiovascular events in individuals suffering from acute coronary syndrome (ACS) and in patients undergoing percutaneous coronary intervention (PCI), the data, studied until now, covers only a minute fraction of the genetic variations of the human genome.  Using two-stage large-scale sequencing data which consists of high-depth exome sequencing of 168 patients in the discovery cohort and 1793 patients of the replication cohort being subjected to high-depth targeted sequencing, Lie and colleagues discovered novel variants that show associations with major cardiovascular events in a 1.5 year-long follow-up. MYOM2 (rs17064642), ECHS1 (rs140410716), AGAP3 (rs75750968), WDR24 (rs11640115), EFR3A (rs4736529), NECAB1 (rs74569896), ZDHHC3 (rs3749187), and KRTAP10-4 (rs201441480) were the 8 novel genotypes that we found to bear associations with major cardiovascular adverse effects in patients with ACS. MYOM2 and ECHS1, interestingly, were downregulated both in human and animal models with adverse effect-related phenotypes. With AUC ranges between 0.92 and 0.94 for three machine-learning methods, Liu and colleagues were able to develop a superior classifier for predicting these adverse events over a period of 18 months. Their findings bring focus to predicting cardiovascular adverse outcomes and can aid clinicians in optimizing pharmacological intervention while treating patients suffering from ACS. Pharmacogenomics J. 2021 Dec;21(6):664-672.