APOE Genotype and Statin Response: Evidence from the UK Biobank Baseline Assessment and Linked Mortality Data

Abstract

IntroductionAPOE genotype may influence response to statin therapy. We examined the relationship between APOE genotype, statin use, lipid biomarkers and mortality using data from the UK Biobank. MethodsUK Biobank baseline assessment data and linked mortality records (389,843-452,189 participants) were analysed. Linear regression and Cox proportional hazards models assessed associations between APOE genotype, statin use, and lipid biomarkers (Apolipoprotein A, Apolipoprotein B, HDL cholesterol [HDLC], LDL cholesterol [LDLC], Lipoprotein A, Total Cholesterol, Triglycerides) as well as mortality, adjusting for clinical and genetic covariates. ResultsSignificant interactions between APOE genotype and statin use were observed for most lipid biomarkers at the Bonferroni-adjusted threshold (P < 0.007), including Apolipoprotein A (P = 0.0065), Apolipoprotein B (P < 2.00e-16), LDLC, Total Cholesterol, and Triglycerides (all P < 2.00e-16), and HDLC (P = 0.0001). Lipoprotein A was not significant (P = 0.104). Population-level trends did not always translate to individual outcomes; for example, statin-treated{varepsilon} 4{varepsilon}4 carriers showed significant LDLC reductions but their LDLC levels remained higher than those of untreated{varepsilon} 2{varepsilon}2 individuals. APOE genotype was significantly associated with all-cause death (trend P < 2.00e-16) and cardiovascular-related death (P = 1.55e-10). The{varepsilon} 4{varepsilon}4 genotype had the highest risk, with respective hazard ratios of 1.51 (95% CI: 1.41- 1.62) and 1.54 (1.33-1.77). However, the APOE:statin use interaction was not significant. ConclusionThe APOE genotype influences lipid biomarker levels, with statin use associated with favourable changes across all genotypes. The magnitude of these changes depends on both the APOE genotype and baseline lipid levels.