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Published on: October 12, 2017
Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I
Marie-Claude Blatter Garin1, Xenia Moren, Richard W James
1Clinical Diabetes Unit, Division of Endocrinology, Diabetes, and Nutrition, Medical Faculty, University Hospital, 1211 Geneva 14, Switzerland.
Insights
Paraoxonase-1 (PON1) impacts high-density lipoprotein (HDL) levels, with this association weakened in coronary disease patients. Genetic variations in the PON1 gene promoter influence HDL concentrations, but this effect diminishes in those with heart conditions.
Area of Science:
- Biochemistry
- Cardiovascular Genetics
Background:
- Paraoxonase-1 (PON1) is closely linked with high-density lipoprotein (HDL) in plasma.
- This association is hypothesized to be necessary for PON1's interaction with hydrophobic complexes.
Purpose of the Study:
- To investigate the association between Paraoxonase-1 (PON1) and high-density lipoprotein (HDL) in individuals with coronary artery disease and age-matched controls.
- To explore the influence of PON1 gene polymorphisms on HDL concentrations in health and disease.
Main Methods:
- Assessed PON1 activities and concentrations in relation to HDL-cholesterol and apolipoprotein A-I (apoA-I) levels.
- Examined the impact of PON1 gene promoter (C-107 T) and coding region (Q192R, L55M) polymorphisms on HDL parameters.
- Utilized multivariate analyses to determine independent predictors of HDL concentrations.
Main Results:
- Significant positive correlations were found between PON1 levels and HDL-cholesterol/apoA-I in both cases and controls.
- The relationship between PON1 and HDL was less effective in coronary cases compared to controls.
- The PON1 promoter polymorphism C-107 T significantly influenced HDL concentrations in controls but not in coronary cases.
- The promoter polymorphism was an independent determinant of HDL levels.
Conclusions:
- PON1 influences plasma HDL concentrations.
- Detrimental modifications in the PON1-HDL relationship are observed in individuals with coronary artery disease.
- PON1 gene promoter variations play a role in determining HDL levels, particularly in the absence of heart disease.
Abstract:
Paraoxonase-1 (PON1) and HDL are tightly associated in plasma, and this is generally assumed to reflect the need for the enzyme to associate with a hydrophobic complex. The association has been examined in coronary cases and age-matched controls. Highly significant (P < 0.0001), positive associations were observed between PON1 activities and concentrations and HDL-cholesterol and apolipoprotein A-I (apoA-I) concentrations in cases and controls. Corrected slopes were significantly different in cases (cases vs. controls: arylesterase, r = 0.19 vs. 0.38, P < 0.02 for apoA-I and r = 0.15 vs. 0.34, P < 0.02 for HDL-cholesterol) such that if PON1 should influence serum HDL, it would be less effective in coronary cases. When examined as a function of the PON1 gene promoter polymorphism C-107 T, highly significant differences (P < 0.001) in HDL-cholesterol and apoA-I were observed between genotypes for controls, with high expresser alleles having the highest HDL concentrations. This relationship was lost in cases with coronary disease. The coding region polymorphisms Q192R and L55M of the PON1 gene showed no association with HDL. The promoter polymorphism was an independent determinant of HDL concentrations in multivariate analyses. These data are consistent with an impact of PON1 on plasma concentrations of HDL, with detrimental modifications to the relationship in coronary cases.
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