Genetics
ApoE4 allele blunts the correlation between CETP activity and LDL cholesterol during colestipol and lovastatin treatment (Eur J Clin Pharmacol 1999)
Original title: The effect of the apolipoprotein E phenotype on cholesteryl ester transfer protein activity, plasma lipids and apolipoprotein A I levels in hypercholesterolaemic patients on colestipol and lovastatin treatment
Patients with type IIa or IIb hypercholesterolaemia were treated with colestipol or lovastatin, with plasma CETP activity measured alongside lipids and apolipoprotein A-I and related to apoE phenotype. Baseline CETP activity averaged 114 nmol per hour per milliliter, and neither lipid levels, apo A-I, nor CETP activity differed significantly by apoE phenotype, though HDL cholesterol and apo A-I were lower in apoE4/4 patients and higher in other phenotypes. CETP activity correlated significantly with LDL cholesterol concentration (r=0.52, P=0.01) and with the LDL cholesterol reduction during colestipol (r=0.51, P=0.02) and lovastatin (r=0.65, P=0.001) treatment, but only in patients lacking the apoE4 allele. Colestipol and lovastatin reduced CETP activity to a similar degree regardless of apoE phenotype, but apoE phenotype modified the interaction between CETP activity and LDL cholesterol both at baseline and during pharmacological cholesterol lowering.
Original abstract
Background: Apolipoprotein E (apo E) allele E 4 is associated with high atherogenic lipid levels and coronary heart disease. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from (high density lipoprotein) HDL to other lipoproteins. CETP gene expression is enhanced in hypercholesterolaemia and correlates with plasma apo E concentration.
Objective: The effect of the apo E phenotype on plasma CETP activity and the hypolipidaemic efficacy of colestipol and lovastatin was studied in patients with type II a or II b hypercholesterolaemia.
Results: The baseline mean plasma total, low density lipoprotein (LDL) and HDL cholesterol, triglyceride, apolipoprotein A I (apo A I) concentrations and CETP activity were 8.89 mmol x l(-1), 6.78 mmol x l(-1), 1.39 mmol x l(-1), 1.59 mmol x l(-1), 1.49 g x l(-1) and 114 nmol x h(-1) x ml(-1), respectively. The colestipol-induced changes were -26%, -36%, +5%, + 12%, -1% and -17%, and the lovastatin-induced changes -34%, -44%, +6%, -18%, +1% and -19%. The lipid and apo A I concentrations or the CETP activity did not differ statistically significantly according to the apo E phenotype, although the HDL cholesterol and apo A I levels were lowered in patients with apo E 4/4 but elevated in patients with the other phenotypes. The CETP activity correlated with the LDL cholesterol concentration (r = 0.52, P = 0.01) and the change in the LDL cholesterol during colestipol (r = 0.51, P = 0.02) and lovastatin (r = 0.65, P = 0.001) treatment, but only in patients without the apo E 4 allele.
Conclusion: Colestipol and lovastatin reduced CETP activity to the same amount, regardless of the apo E phenotype. The apo E phenotype seems to modify the interaction between CETP activity and LDL cholesterol in hypercholesterolaemia and during pharmacological lowering of cholesterol.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.