Genetics
CETP TaqIB B2B2 genotype blunts cholesterol-lowering response to simvastatin in Thai patients (Cardiovasc Ther 2017)
Original title: The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients
Two hundred and twenty-five Thai patients with hypercholesterolemia were treated with simvastatin 20 or 40 mg daily for three months, and genotyped for APOE, CETP TaqIB, and PCSK9 polymorphisms to assess their effect on lipid-lowering response. Carriers of the CETP TaqIB B2B2 genotype showed a smaller reduction in total cholesterol (minus 16.37 percent versus minus 24.92 percent, P = .016) and LDL-C (minus 22.54 percent versus minus 35.19 percent, P = .028) than B1 carriers. APOE4 carriers likewise showed a blunted response compared with APOE2 and APOE3 carriers, while PCSK9 474IV carriers responded more strongly than 474II carriers. Individuals carrying more of these risk alleles combined had progressively smaller cholesterol reductions in response to simvastatin.
Original abstract
Aim: To investigate the effect of apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and proprotein convertase subtilisin kexin type 9 (PCSK9) polymorphisms on the lipid-lowering response to simvastatin therapy in Thai hypercholesterolemic patients.
Method: Two hundred and twenty-five hypercholesterolemic patients in southern Thailand were enrolled and treated with simvastatin 20 or 40 mg per day for 3 months. Serum lipids were measured before and after the therapy. APOE, CETP TaqIB, and PCSK9 (R46L, I474V, and E670G) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: After 3 months of simvastatin therapy, subjects with APOE2 (Total cholesterol [TC]: -30.89% vs-13.56%, P < .05, LDL-C: -45.00% vs -17.73%, P < .05) and APOE3 carriers (TC: -26.22% vs -13.56%, P < .05, LDL-C: -37.14% vs -17.73%, P < .05) had greater TC and LDL-C reduction compared to APOE4 carriers, whereas CETP TaqIB B2B2 genotype showed lower TC (-16.37% vs -24.92%, P = .016) and LDL-C (-22.54% vs -35.19%, P = .028) reduction compared to CETP TaqIB B1 carriers. In addition, PCSK9 474IV carriers showed greater LDL-C (-50.57% vs -32.99%) reduction compared to PCSK9 474II carriers. Combined effect analyses showed that individuals carrying more risk alleles tended to have lower TC and LDL-C (P for trend = .000 and .000, respectively) reduction in response to simvastatin therapy.
Conclusion: APOE4 carriers and the CETP TaqIB B2B2 genotype were associated with a decreased response, but PCSK9 474IV carriers tended to be associated with an increased response to simvastatin therapy in Thai hypercholesterolemic patients.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.