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


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.
Sardo
Maria Adriana
MA
Department of Internal Medicine, School of Medicine, University of Messina, Azienda Ospedaliera Universitaria, 'G. Martino', Messina, Italy.
Campo
Salvatore
S
Bonaiuto
Michele
M
Bonaiuto
Antonio
A
Saitta
Carlo
C
Trimarchi
Giuseppe
G
Castaldo
Maria
M
Bitto
Alessandra
A
Cinquegrani
Maurizio
M
Saitta
Antonino
A
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000187:drug effects*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D010919:Placebos; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D014810:Vitamin E / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D010919:Placebos; D011758:Pyrroles; D014810:Vitamin E; D000069059:Atorvastatin; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human