Genetics
Patients with atherogenic CETP genotypes get more HDL and triglyceride benefit from high-dose atorvastatin, DALI trial finds (Diabetes Care 2003)
Original title: Common cholesteryl ester transfer protein gene polymorphisms and the effect of atorvastatin therapy in type 2 diabetes
This 30-week randomized double-blind placebo-controlled DALI trial tested whether CETP gene variations modify the effect of lipid-lowering treatment in type 2 diabetes, comparing atorvastatin 10 mg and 80 mg in 217 unrelated diabetic patients genotyped for CETP TaqIB and A-629C (found tightly concordant, P less than 0.001). At baseline, B1B1 carriers had lower HDL-cholesterol (0.99 vs 1.11 mmol/L, P less than 0.05) and higher CETP mass (2.62 vs 2.05 mg/L, P less than 0.001) than B2B2 carriers. Atorvastatin dose-dependently reduced CETP mass by 18% (10 mg) and 29% (80 mg) versus placebo (both P less than 0.001). CETP TaqIB genotype modified the atorvastatin response: HDL-cholesterol elevation was 7.2% in B1B1, 6.1% in B1B2, and 0.5% in B2B2 (P less than 0.05), with similar trends for triglyceride and CETP mass reduction. The authors conclude B1B1/CC carriers, who have a more atherogenic lipid profile, respond better to statin therapy.
Original abstract
Objective: The cholesteryl ester transfer protein (CETP) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles. Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes.
Research Design And Methods: We performed a 30-week randomized double-blind placebo-controlled trial with atorvastatin 10 mg (A10) and 80 mg (A80) in 217 unrelated patients with diabetes.
Results: CETP TaqIB and A-629C polymorphisms were tightly concordant (P < 0.001). At baseline, B1B1 carriers had lower plasma HDL cholesterol (0.99 +/- 0.2 vs. 1.11 +/- 0.2 mmol/l, P < 0.05), higher CETP mass (2.62 +/- 0.8 vs. 2.05 +/- 0.4 mg/l, P < 0.001), and slightly increased, though not significant, plasma TGs (2.7 +/- 1.05 vs. 2.47 +/- 0.86, P = 0.34) compared with B2B2 carriers. Atorvastatin treatment significantly reduced CETP mass dose-dependently by 18% (A10) and 29% (A80; both vs. placebo P < 0.001, A10-A80 P < 0.001). CETP mass and activity were strongly correlated (r = 0.854, P < 0.0001). CETP TaqIB polymorphism appeared to modify the effect of atorvastatin on HDL cholesterol elevation (B1B1 7.2%, B1B2 6.1%, B2B2 0.5%; P < 0.05), TG reduction (B1B1 39.7%, B1B2 38.4%, B2B2 18.4%; P = 0.08), and CETP mass reduction (B1B1 32.1%, B1B2 29.6%, B2B2 21.9%; P = 0.27, NS). Similar results were obtained for the A-629C polymorphism.
Conclusions: In conclusion, the B1B1/CC carriers of the CETP polymorphisms have a more atherogenic lipid profile, including low HDL, and they respond better to statin therapy. These results favor the hypothesis that CETP polymorphisms modify the effect of statin treatment and may help to identify patients who will benefit most from statin therapy.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.