Abstract
Background. Paraoxonase-1 (PON1) is the crucial antioxidant marker of high-density lipoproteins. The present study is aimed at assessing the effect of simvastatin treatment on PON1 activity and its relationship to Q192R and M55L polymorphisms in subjects with stable coronary artery disease (CAD). Methods. The patient group was composed of 53 individuals with stable CAD, and the control group included 53 sex-matched police officers without CAD. CAD patients were treated with simvastatin 40mg/day for 12 months. Respectively, flow mediated dilatation (FMD), serum hs-CRP and TNF-α levels, urinary 8-iso-PGF2α concentrations, and PON1 activity were evaluated in definitive intervals. Results. There was no effect of simvastatin treatment on urinary 8-iso-PGF2α. Simvastatin treatment significantly increased FMD value, decreased CRP and TNF-α concentration. After adjusting for PON1 genotypes, significantly higher PON1 activity was noted in the 192R allele carriers, in both groups. Regardless of genotype, PON1 activity remained stable after simvastatin treatment. Conclusions. The present study confirms a positive effect of simvastatin therapy on endothelial function and inflammatory markers in secondary prevention. Simvastatin treatment shows no effects on PON1 activity and 8-isoprostanes level. The effect of simvastatin therapy on PON1 activity is not modulated by Q192R and M55L polymorphisms.
Highlights
Statins reversibly inhibit HMG-CoA reductase, attenuating production of important isoprenoid intermediates used for posttranslational modification of different proteins [1]
The present study aimed to evaluate the association of Q192R and L55M PON1 gene polymorphisms on PON1 activity with and without simvastatin treatment
A relatively low initial mean cardiovascular risk and low baseline total cholesterol and LDL undoubtedly influenced the lipid-lowering effect of simvastatin in the present study
Summary
Statins reversibly inhibit HMG-CoA reductase, attenuating production of important isoprenoid intermediates used for posttranslational modification of different proteins [1]. The overexpression of PON1 in transgenic mice increased the effect of HDL on oxidation and attenuated the rate of formation of atherosclerotic lesions [7, 8]. Some of the polymorphisms significantly affect gene expression and impact serum PON1 concentration. The Q192R polymorphism does not affect the serum PON1 concentration but significantly modifies its activity. The present study is aimed at assessing the effect of simvastatin treatment on PON1 activity and its relationship to Q192R and M55L polymorphisms in subjects with stable coronary artery disease (CAD). Regardless of genotype, PON1 activity remained stable after simvastatin treatment. Simvastatin treatment shows no effects on PON1 activity and 8-isoprostanes level. The effect of simvastatin therapy on PON1 activity is not modulated by Q192R and M55L polymorphisms
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