Genetics
CETP B2B2 homozygotes gain over ten times more HDL cholesterol from simvastatin than B1 carriers, unlike APOE or LIPC genotypes (Clin Chim Acta 2005)
Original title: Pharmacogenetic study of apolipoprotein E, cholesteryl ester transfer protein and hepatic lipase genes and simvastatin therapy in Brazilian subjects
This study investigated whether polymorphisms in APOE, CETP, and hepatic lipase (LIPC), genes with major roles in lipid metabolism, are associated with variable response to statin treatment, prospectively enrolling one hundred forty-six hypercholesterolemic Brazilian patients of European descent treated with simvastatin 20 mg daily for over 6 months (ninety-nine completing follow-up), genotyped by PCR and restriction mapping. After 6 months, no differences in lipid response were observed across APOE or LIPC genotypes. After adjustment for covariates, CETP B2B2 homozygotes showed a significantly greater HDL-cholesterol increase than B1B2 or B1B1 carriers (14.1% vs 1.7% and 1.3%, P less than 0.05). The authors conclude individual HDL-cholesterol response to simvastatin is mediated in part by the CETP gene locus, with B2 homozygotes gaining more benefit than B1 allele carriers.
Original abstract
Background: In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response.
Methods: One hundred forty-six hypercholesterolemic patients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E*2, E*3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping.
Results: After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively).
Conclusion: Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.