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.
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-1Q192R, 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.
Authors: Sarah Jane Mackenzie Ross; Chris Ray Brewin; Helen Valerie Curran; Clement Eugene Furlong; Kelly Michelle Abraham-Smith; Virginia Harrison Journal: Neurotoxicol Teratol Date: 2010-03-20 Impact factor: 3.763
Authors: D L Rainwater; S Rutherford; T D Dyer; E D Rainwater; S A Cole; J L Vandeberg; L Almasy; J Blangero; J W Maccluer; M C Mahaney Journal: Heredity (Edinb) Date: 2008-10-29 Impact factor: 3.821