Effect of Simvastatin Therapy on Paraoxonase Activity and Related Lipoproteins in Familial Hypercholesterolemic Patients

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Abstract
—Human paraoxonase (PON1) is a calcium-dependent esterase closely associated with high density lipoprotein (HDL)-containing apolipoprotein AI (apoAI), which has been shown to confer antioxidant properties to HDL. PON1 has been recently implicated in the pathogenesis of atherosclerosis. Low PON1 activities have been found in familial hypercholesterolemia (FH) and diabetes mellitus. We have undertaken a study of the effect of the lipid-lowering drug simvastatin on serum PON1 activity (in relation to paraoxon and arylesterase activity), on apoAI-containing and apolipoprotein B (apoB)-containing lipoproteins, and on lipid peroxide concentrations in 64 (39 women and 25 men) unrelated FH patients. We have also analyzed the influence of the PON1-192 and PON1-55 genetic polymorphisms on the response of PON1 activity to simvastatin therapy. A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken. The major effect of simvastatin...