| Title: | APOE Genotype and Statin Response: Evidence From the UK Biobank and All of Us Program |
| Journal: | Clinical and Translational Science |
| Published: | 5 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40763922/ |
| DOI: | https://doi.org/10.1111/cts.70314 |
Publication 16026
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Abstract
APOE genotype may affect statin response. Using UK Biobank (UKB) and All of Us (AoU) data, we aimed to investigate associations between APOE genotype, statin use, and key health outcomes. Our analysis included UKB baseline data and linked mortality records (389,843-452,189 participants), and electronic health records (EHR) from 45,515 UKB and 35,562 AoU participants. Multivariable regression and Cox models assessed lipid biomarkers, all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). In UKB, ε3ε4 (HR: 1.08, 95% CI: 1.01-1.15) and ε4ε4 (HR: 1.54, 95% CI: 1.33-1.78) carriers had higher all-cause mortality risk. In AoU, only ε4ε4 carriers showed increased risk (HR: 1.64, 95% CI: 1.08-2.49). Cardiovascular mortality was assessed only in UKB, where ε4ε4 carriers had an increased risk (HR: 1.30, 95% CI: 1.01-1.68). Mortality associations in UKB EHR data were consistent with those from baseline data and linked mortality records (e.g., ε4ε4 genotype: all-cause mortality HR: 1.51, 95% CI: 1.41-1.62; cardiovascular mortality HR: 1.54, 95% CI: 1.33-1.77). However, the statin:APOE interaction term included in the baseline analysis was not statistically significant. In AoU, changes in HDLC, LDLC, and triglycerides were associated with reduced all-cause mortality risk. No significant MACE associations were observed in either cohort. This study reaffirms that APOE ε4 genotype increases mortality risk, including in statin-treated patients, and could therefore be used to inform enhanced monitoring or medication review in these patients.</p>
15 Keywords
- Aged
- Apolipoproteins E
- Biological Specimen Banks
- Cardiovascular Diseases
- Electronic Health Records
- Female
- Genotype
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Male
- Middle Aged
- Risk Factors
- UK Biobank
- United Kingdom
- United States
49 Authors
- Innocent G. Asiimwe
- Andrea L. Jorgensen
- Munir Pirmohamed
- Adam Butterworth
- Alasdair Warwick
- Alba Fernandez-Sanles
- Albert Henry
- Alvina G. Lai
- Amanda Roberts
- Ana Torralbo
- Anoop D. Shah
- Aroon Hingorani
- Arturo Gonzalez-Izquierdo
- Maria Carolina Borges
- Caroline Dale
- Chris Finan
- Claudia Langenberg
- Daniel C. Alexander
- Deborah Lawlor
- Diana Dunca
- Eda B. Ozyigit
- Amand F. Schmidt
- Harry Hemingway
- Honghan Wu
- Jasmine Gratton
- Jean Gallagher
- Jorgen E. Engmann
- Lauren E. Walker
- Victoria L. Wright
- Magdalena Zwierzyna
- Margaret Ogden
- Martin Cox
- Mary Mancini
- Michail Katsoulis
- Mira Hidajat
- Natalie Fitzpatrick
- Nishi Chaturvedi
- Rashmi Kumar
- Rohan Takhar
- Sandesh Chopade
- Simon Ball
- Spiros Denaxas
- Tina Shah
- Valerie Kuan
- Nikita Hukerikar
- Reecha Sofat
- Frances Bennett
- David Ryan
- Maik Pietzner
1 Application
| Application ID | Title |
|---|---|
| 56653 | Pharmacogenomics to improve drug efficacy and safety |
Enabling scientific discoveries that improve human health