APOE Gene Polymorphism as a Determinant of Hyperlipidemia Risk and Effectiveness of Statin Drug Therapy

Introduction: Hyperlipidemia is a medical condition characterized by high levels of lipids, including total cholesterol, low-density lipoprotein (LDL), and triglycerides in the blood. This condition plays a major role in the pathogenesis of cardiovascular diseases, such as atherosclerosis, coronary heart disease, and stroke, which are the leading causes of death and disability globally. The risk factors for hyperlipidemia involve a complex interaction between environmental, lifestyle, and genetic factors. Among these genetic factors, the apolipoprotein E ( APOE ) gene has long been identifi ed as one of the major determinants of lipid metabolism. This study aims to analyze the impact of APOE gene polymorphisms on hyperlipidemia risk and statin therapy response using a bioinformatics approach, providing insights into personalized lipid-lowering treatments. Material and methods: This study used a bioinformatics approach to analyze genetic and clinical data available in several database sources, including PharmGKB, Ensembl, and GTEx Portal. Results: APOE gene polymorphisms play a signifi cant role in determining the risk of hyperlipidemia and the effectiveness of statin therapy. Genetic variations such as rs7412, rs429358, rs449647, and rs71352238 affect lipid metabolism and patient response to various types of statins, including atorvastatin, pravastatin, simvastatin, and rosuvastatin. The results showed that individuals with certain genotypes, such as CT or TT, tend to have a better response to lowering LDL-C levels compared to other genotypes. Conversely, some alleles, such as the C allele in rs7412 and rs429358, are associated with lower therapy response or increased cardiovascular risk, but these risks can be reduced by selecting appropriate therapy, such as simvastatin. Conclusions: Pharmacogenomic approaches may guide more personalized management of statin therapy to improve clinical outcomes and minimize the risk of side effects. This study highlights the importance of understanding genetic interactions in the management of hyperlipidemia to prevent broader cardiovascular complications.