APOE genotype and the effect of statins: a systematic review and meta-analysis

Abstract

Introduction: The APOE genotype may affect statin therapy response. We conducted a systematic review and meta-analysis to update and quantify this association across various outcomes. Methods: We searched seven databases (MEDLINE, Scopus, Web of Science, The Cochrane Library, APA PsycINFO, CINAHL Plus, and ClinicalTrials.gov) on 9th May 2024. Screening and data extraction were performed by two reviewers and a machine learning tool (ASReview). Results: From 4,352 de-duplicated records, 68 studies were included in the systematic review and 52 in the meta-analysis. Biomarkers analysed included Low-Density Lipoprotein Cholesterol (LDLC), Total Cholesterol (TC), Triglycerides (TG), and High-Density Lipoprotein Cholesterol (HDLC). Compared to ε3 carriers, ε2 carriers showed greater reductions in LDLC (mean difference: -2.98%, 95% CI: -5.88% to -0.08%) and similar reductions in TC (-2.73%, -5.62% to 0.16%), and TG (-4.95%, -11.93% to 2.04%) with no significant difference in HDLC (-0.09%, -3.10% to 2.91%). After adjusting for publication bias, ε4 carriers showed less pronounced statin effects, with smaller reductions in LDLC (mean difference: 10.04%, 6.04% to 14.04%), TC (8.99%, 5.08% to 12.90%), and TG (8.24%, 2.15% to 14.33%), along with a smaller increase in HDLC (-10.08%, -15.30% to -4.85%) compared to ε3 carriers. Study quality was uncertain, and heterogeneity (partly explained by sex and Familial Hypercholesterolemia) was high, especially for the percentage changes. A stronger genotype effect was seen in males. Conclusion: Our meta-analysis shows that APOE genotype can significantly influence statin response, emphasizing the need to incorporate known genetic factors into personalized treatment regimes.