Genetics
CETP genetic variants shape the lipid response to statins in Alzheimer's disease patients (Sao Paulo Med J 2025)
Original title: Associations between selected genetic variants and lipid profile variability in response to statins in Alzheimer's disease: a prospective observational study
In a prospective pharmacogenetic study of 189 outpatients with Alzheimer's disease at the Universidade Federal de Sao Paulo, researchers followed lipid profile changes over one year of statin therapy and tested associations with cholesterol-metabolism-related genetic variants including two CETP polymorphisms, rs5882 and rs708272, alongside APOE, LDLR, HMGCR, NR1H2 and ACE variants. Statins lowered total and LDL cholesterol overall, with effects on HDL cholesterol varying by statin used. Carriers of the rs5882-A and rs708272-A CETP variants benefited most from statins, showing lower total cholesterol, higher HDL cholesterol, and with atorvastatin lower triglycerides, whereas carriers of rs5882-GG and rs708272-GG showed more pronounced total and LDL cholesterol lowering with atorvastatin, indicating CETP genotype shapes the lipid response to statin therapy in this population.
Original abstract
Background: Lipid profiles are largely determined by genetic variants, and lipid metabolism plays a crucial role in Alzheimer's disease.
Objective: To investigate whether lipid profile variability in response to diverse statins could be affected by cholesterol metabolism-related genetic variants in Alzheimer's disease..
Design And Setting: This prospective observational pharmacogenetic study was conducted at the Universidade Federal de São Paulo (Unifesp), Brazil.
Methods: Consecutive outpatients were prospectively followed for lipid profile variations over one year, estimated by the associations between statin therapy and the following variants: rs2695121 (NR1H2), rs3846662 (HMGCR), rs11669576 (LDLR8), rs5930 (LDLR10), rs5882 and rs708272 (CETP), rs7412 and rs429358 (APOE), and ACE insertion/deletion polymorphism.
Results: All polymorphisms in the 189 patients were in Hardy-Weinberg equilibrium. Statins resulted in lower total cholesterol and LDL cholesterol levels, whereas the effects on HDL cholesterol varied according to the statin used. Atorvastatin resulted in lower triglyceride level variations than simvastatin. APOE-ε4 carriers showed a better response to atorvastatin in elevating HDL-cholesterol than APOE-ε4 non-carriers. Carriers of the ACE insertion allele had cumulatively lower total cholesterol and LDL-cholesterol levels, regardless of statin therapy, but lower triglyceride levels when using atorvastatin. Carriers of rs11669576-G had lower total cholesterol and LDL-cholesterol levels when using simvastatin, and lower total cholesterol and triglycerides when using atorvastatin. Concerning CETP haplotypes, carriers of rs5882-A and rs708272-A benefitted the most from statins, which lowered total cholesterol and increased HDL-cholesterol levels, and from atorvastatin lowering triglycerides; however, the effects of atorvastatin lowering total cholesterol and LDL-cholesterol were more pronounced for carriers of rs5882-GG/rs708272-GG.
Conclusion: Lipid profile variations may be pharmacogenetically mediated in Alzheimer's disease, thus, confirming their high heritability.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.