Genetics
CETP genetic variants predict how much LDL cholesterol falls with statin therapy (Pharmacogenomics J 2020)
Original title: Genetic contribution to lipid target achievement with statin therapy: a prospective study
In a prospective, multicenter study of 252 patients treated with simvastatin, atorvastatin or rosuvastatin, researchers examined whether variants in CETP, ABCA1, CYP2D6 and CYP2C9 affected achievement of LDL cholesterol or non-HDL cholesterol treatment targets. Carriers of the ABCA1 variant rs2230806 and CYP2D6*3 were less likely to reach therapeutic lipid targets (P equals 0.020 and P equals 0.040 respectively). Among CETP variants, carriers of rs708272 showed a 10.56% smaller LDL cholesterol reduction with rosuvastatin (P equals 0.028), while carriers of rs5882 showed a 13.33% greater LDL cholesterol reduction (P equals 0.032), suggesting that if confirmed, CETP genotyping alongside ABCA1 and CYP2D6 could help personalise statin choice and dosage.
Original abstract
Statin therapy response is highly variable. Variants of lipid metabolism genes and statin pharmacokinetic modulators could play a role, however, the impact of most of these variants remains unconfirmed. A prospective and multicenter study included 252 patients was carried out in order to assess, according to achievement of LDL-C or non-HDL-C therapeutic targets and quantitative changes in lipid profiles, the impact of CETP, ABCA1, CYP2D6, and CYP2C9 gene candidate variants on the simvastatin, atorvastatin, and rosuvastatin response. Patients carrier ABCA1 rs2230806 and CYP2D6*3 variants are less likely to achieve therapeutic lipid targets (p = 0.020, OR = 0.59 [0.37, 0.93]; p = 0.040, OR = 0.23 [0.05, 0.93], respectively). Among CETP variants, rs708272 was linked to a 10.56% smaller reduction in LDL-C with rosuvastatin (95% CI = [1.27, 19.86] %; p = 0.028). In contrast, carriers of rs5882 had a 13.33% greater reduction in LDL-C (95% CI = [25.38, 1.28]; p = 0.032). If these findings are confirmed, ABCA1, CYP2D6, and CETP genotyping could be used to help predict which statin and dosage is appropriate in order to improve personalized medicine.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.