| 15969877 |
Sardo MA, Campo S, Bonaiuto M, Bonaiuto A, Saitta C, Trimarchi G, Castaldo M, Bitto A, Cinquegrani M, Saitta A: Antioxidant effect of atorvastatin is independent of PON1 gene T (-107) C, Q192R and L55M polymorphisms in hypercholesterolaemic patients. Curr Med Res Opin. 2005 May;21(5):777-84.
BACKGROUND: 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. |
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