Common Cholesteryl Ester Transfer Protein Gene Polymorphisms and the Effect of Atorvastatin Therapy in Type 2 Diabetes
- 1 April 2003
- journal article
- clinical trial
- Published by American Diabetes Association in Diabetes Care
- Vol. 26 (4), 1216-1223
- https://doi.org/10.2337/diacare.26.4.1216
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.Keywords
This publication has 28 references indexed in Scilit:
- A novel cholesteryl ester transfer protein promoter polymorphism (−971G/A) associated with plasma high-density lipoprotein cholesterol levelsAtherosclerosis, 2002
- The Effect of Aggressive Versus Standard Lipid Lowering by Atorvastatin on Diabetic DyslipidemiaDiabetes Care, 2001
- Association of Cholesteryl Ester Transfer Protein– Taq IB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease RiskArteriosclerosis, Thrombosis, and Vascular Biology, 2000
- New Functional Promoter Polymorphism, CETP/−629, in Cholesteryl Ester Transfer Protein (CETP) Gene Related to CETP Mass and High Density Lipoprotein Cholesterol LevelsArteriosclerosis, Thrombosis, and Vascular Biology, 2000
- Sex-Dependent Association of a Genetic Polymorphism of Cholesteryl Ester Transfer Protein with High-Density Lipoprotein Cholesterol and Macrovascular Pathology in Type II Diabetic PatientsJournal of Clinical Endocrinology & Metabolism, 1999
- Mass Concentration of Plasma Phospholipid Transfer Protein in Normolipidemic, Type IIa Hyperlipidemic, Type IIb Hyperlipidemic, and Non–Insulin-Dependent Diabetic Subjects as Measured by a Specific ELISAArteriosclerosis, Thrombosis, and Vascular Biology, 1999
- Sterol Regulatory Element Binding Protein-1 Activates the Cholesteryl Ester Transfer Protein Gene in Vivobut Is Not Required for Sterol Up-regulation of Gene ExpressionPublished by Elsevier BV ,1998
- Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controlsAtherosclerosis, 1996
- Transfer proteins in reverse cholesterol transportCurrent Opinion in Lipidology, 1992
- Different locations of cholesteryl ester transfer protein and phospholipid transfer protein activities in plasmaAtherosclerosis, 1991