Genetic and environmental determinants of the PON-1 phenotype.
| Autor: | Roest M; Research Laboratory, Department of Clinical Chemistry, University Medical Center Utrecht, The Netherlands. m.roest@azu.nl, van Himbergen TM, Barendrecht AB, Peeters PH, van der Schouw YT, Voorbij HA |
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| Jazyk: | angličtina |
| Zdroj: | European journal of clinical investigation [Eur J Clin Invest] 2007 Mar; Vol. 37 (3), pp. 187-96. |
| DOI: | 10.1111/j.1365-2362.2007.01769.x |
| Abstrakt: | Background: Paraoxonase (PON-1) is a high-density lipoprotein (HDL)-associated enzyme that may protect against cardiovascular disease (CVD), because it hydrolyses oxidized phospholipids of low-density lipoprotein (LDL) and therefore prevents the detrimental effects on the arterial wall. The current report describes the determinants of PON-1 bioavailability and activity. Materials and Methods: This is the largest (n = 1527) cross-sectional evaluation performed on PON-1 genotypes (Q192R, T-107C and L55M) and environmental determinants to PON-1 catalytic activity and bioavailability in serum of postmenopausal women. PON-1 catalytic activity and PON-1 bioavailability were measured, in vitro, with a paraoxon hydrolysis assay and a phenylacetate hydrolysis assay, respectively. Results: The major determinant of paraoxon hydrolytic activity is the Q192R genotype, but there was also a relation with the C-107T and L55M genotype, HDL levels and alcohol consumption. Phenylacetate hydrolytic activity was most strongly affected by the C-107T genotype followed by the L55M genotype, HDL levels, alcohol consumption and smoking. Conclusions: PON-1 Q192R, C-107T and L55M genotype, alcohol consumption, smoking and HDL levels are determinants of serum PON-1 phenotype. The contributions of the genetic markers to the PON-1 phenotype are stronger than the contributions of the lifestyle determinants. |
| Databáze: | MEDLINE |
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