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

Hossein Z. Mirdamadi, Ferenc Sztanek, Zoltan Derdak, I. Seres, M. Harangi, G. Paragh

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)366-374
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume66
Issue number3
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Aryldialkylphosphatase
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Phenotype
Lipids
Simvastatin
fluvastatin
human PON1 protein
Therapeutics
Lipid Peroxides
Apolipoproteins B
Hypercholesterolemia
Serum
Genes
Lipoproteins
Atherosclerosis
Triglycerides

Keywords

  • High-density lipoprotein
  • Low-density lipoprotein
  • Paraoxonase
  • Phenotype
  • Statin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters. / Mirdamadi, Hossein Z.; Sztanek, Ferenc; Derdak, Zoltan; Seres, I.; Harangi, M.; Paragh, G.

In: British Journal of Clinical Pharmacology, Vol. 66, No. 3, 09.2008, p. 366-374.

Research output: Contribution to journalArticle

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AU - Mirdamadi, Hossein Z.

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AU - Seres, I.

AU - Harangi, M.

AU - Paragh, G.

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N2 - 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.

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