Wanmasae S, et al. – This study assessed the lipid–lowering response to simvastatin therapy in association with the presence of apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and proprotein convertase subtilisin kexin type 9 (PCSK9) polymorphisms in hypercholesterolemic patients. Findings showed that response to simvastatin therapy was decreased in association with the presence of APOE4 and the CETP TaqIB B2B2 genotype, whereas, increased in PCSK9 474IV carriers.

Methods

• In this study, 225 hypercholesterolemic patients in Southern Thailand were enrolled and treated with simvastatin 20 or 40 mg per day for 3 months.
• Researchers measured serum lipids before and after the therapy.
• They analyzed APOE, CETP TaqIB, and PCSK9 (R46L, I474V, and E670G) polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP).

Results

• Findings demonstrated that after 3 months of simvastatin therapy, subjects with APOE2 (TC: -30.89% vs.-13.56%, p < 0.05, LDL-C: -45.00% vs. -17.73%, p < 0.05) and APOE3carriers (TC: -26.22% vs. -13.56%, p < 0.05, LDL-C: -37.14% vs. -17.73%, p < 0.05) had greater TC and LDL-C reduction compared to APOE4 carriers, whereas CETP TaqIB B2B2 genotype demonstrated lower TC (-16.37% vs.-24.92%, p = 0.016) and LDL-C (-22.54% vs. -35.19%, p = 0.028) reduction compared to CETP TaqIB B1 carriers.
• In addition, researchers observed that PCSK9 474IV carriers exhibited greater LDL-C (-50.57% vs. -32.99%) reduction compared to PCSK9 474II carriers.
• According to data, it was evident in combined effect analyses that individuals carrying more risk alleles tended to have lower TC and LDL-C (p for trend = 0.000 and 0.000, respectively) reduction in response to simvastatin therapy.