Antioxidant effect of atorvastatin is independent of PON1 gene T(–107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients

Abstract

ABSTRACTBackground: Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity has been reported following statin treatment.Objective: In the present study the following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(–107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment.Research design and methods: 205 Sicilian subjects with primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were concurrently enrolled. Hypercholesterolaemic patients were randomly divided into two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group. Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase, oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in LDL, PON1 activity and genotypes in both HCh and control subjects were determined at baseline. The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups.Results: HCh subjects showed significantly lower LDL resistance to oxidation, vitamin E content and PON1 activity levels than controls. A strong association was found among PON1 T(–107)C genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity. After treatment, the atorvastatin group displayed a significant decrease in total cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an increase in vitamin E content and PON1 activity, compared with baseline values. Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed.Conclusions: These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism.