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