The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • It has been suggested that the human paraoxonase-1 (PON1) genotype is an important determinant of the therapeutic response given to statin treatment. • It is also known that the PON1 activity status is a better predictor of coronary heart disease risk than any of the known PON1 genotypes. • Our goal was to answer this previously uninvestigated, still clinically relevant question: does the PON1 phenotype have an impact on the paraoxonase-activating and lipid-lowering effect of different types of statins. WHAT THIS STUDY ADDS • All the statins (atorvastatin, simvastatin and fluvastatin) included in this study were able to increase serum paraoxonase activity and decrease triglyceride levels effectively; however, this response seemed to be more significant in patients with AB+BB PON1 phenotype than in those bearing AA PON1 phenotype. • Furthermore, the apolipoprotein B-lowering effect of atorvastatin was also found to be PON1 phenotype-dependent. • Our results indicate that the PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters. Aims Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters. Methods One hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day−1 atorvastatin, 10/20 mg day−1 simvastatin and 80 mg day−1 extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method. Results Three months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group. Conclusions The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.