Antioxidant effect of atorvastatin is independent of PON1 gene T(–107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients
| Autor: | Alessandra Bitto, Antonino Saitta, Michele Bonaiuto, Maurizio Cinquegrani, Antonio Bonaiuto, Carlo Saitta, M.A. Sardo, Maria Castaldo, Salvatore Campo, Giuseppe Trimarchi |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Antioxidant Statin medicine.drug_class medicine.medical_treatment Atorvastatin Hypercholesterolemia Placebos Internal medicine Oxidation medicine TBARS Humans Vitamin E Pyrroles Promoter Regions Genetic PON1 Polymorphism Genetic medicine.diagnostic_test Aryldialkylphosphatase business.industry Anticholesteremic Agents nutritional and metabolic diseases Cholesterol LDL Low-density lipoprotein (LDL) Serum paraoxonase General Medicine Middle Aged Endocrinology Heptanoic Acids Female lipids (amino acids peptides and proteins) business Lipid profile Oxidation-Reduction Lipoprotein medicine.drug |
| Zdroj: | Current Medical Research and Opinion. 21:777-784 |
| ISSN: | 1473-4877 0300-7995 |
| Popis: | 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.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.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.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.These results show, for the first time, that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism. |
| Databáze: | OpenAIRE |
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