Genome-Wide and Exome-Wide Significant Genetic Variants Influencing Rosuvastatin Therapy: A Scoping Review

Background Cardiovascular diseases remain the leading cause of mortality worldwide, with elevated low-density lipoprotein cholesterol representing a major risk factor. Rosuvastatin is widely used for cardiovascular prevention due to its potent lipid-lowering effects. Significant interindividual variability exists in its pharmacokinetics (PK), pharmacodynamic (PD) response, and susceptibility to adverse effects, which is not fully understood. Objective Genome-wide association studies (GWAS) and exome-wide association studies (ExWAS) have emerged as powerful approaches to identify genetic determinants that influence drug response. This review aimed to summarize evidence from such studies investigating the influence of genetic variation on rosuvastatin PK, PD, and intolerance. Design A systematic literature search was performed in PubMed and Web of Science to identify GWAS and ExWAS studies examining associations between single-nucleotide polymorphisms (SNPs) and rosuvastatin PK, PD, or intolerance. Eligible English-language studies published up to July, 2025 were independently screened by two reviewers, and data were extracted from the included studies. Results Six eligible studies were included, and relevant data were extracted. Genome-wide significant associations were observed for SLCO1B1 , affecting rosuvastatin plasma concentrations, while variants in ABCG2, LPA, APOE , and PCSK9 were linked to PD effects. Common variants in TMEM9 and KLF12 were associated with rosuvastatin intolerance. Additional SNPs were identified at sub-genome-wide or exome-wide significance levels. Conclusion Limitations across studies included treatment with different statins and small sample sizes, which may obscure conclusions. Overall, these findings highlight the potential of pharmacogenomic research to guide personalized rosuvastatin therapy by identifying individuals at higher risk of altered drug response or adverse events.