Genetic and environmental determinants of the PON-1 phenotype.
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.


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.
Roest
M
M
Research Laboratory, Department of Clinical Chemistry, University Medical Center Utrecht, The Netherlands. m.roest@azu.nl
van Himbergen
T M
TM
Barendrecht
A B
AB
Peeters
P H M
PH
van der Schouw
Y T
YT
Voorbij
H A M
HA
D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003430:Cross-Sectional Studies; D005260:Female; D033141:Genetic Determinism; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*
D002791:Cholesterol, Dietary; D005819:Genetic Markers; D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase