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- Title
Genetic and environmental determinants of the PON-1 phenotype.
- Authors
Roest, M.; van Himbergen, T. M.; Barendrecht, A. B.; Peeters, P. H. M.; van der Schouw, Y. T.; Voorbij, H. A. M.
- Abstract
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.
- Subjects
CARDIOVASCULAR diseases; PARAOXONASE; HIGH density lipoproteins; SERUM; ALCOHOL drinking; SMOKING
- Publication
European Journal of Clinical Investigation, 2007, Vol 37, Issue 3, p187
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/j.1365-2362.2007.01769.x