Submitted on July 5, 2005
Revised on November 22, 2005
Accepted on December 2, 2005
Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I
Marie-Claude Blatter Garin, Xenia Moren, and Richard W. James
Endocrinology, Diabetes and Nutrition, Geneva Medical School, Geneva 11 1211
Corresponding Author: Richard.James{at}hcuge.ch
Paraoxonase-1 and HDL are tightly associated in plasma and it 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 paraoxonase-1 activities and concentrations, with HDL-cholesterol and apolipoprotein A-I (apoA-I) concentrations in cases and controls. Corrected slopes were significantly different in cases (cases v controls; arylesterase, r= 0.19 v 0.38, p<0.02 for apoA-I and r=0.15 v 0.34, p<0.02 for HDL-cholesterol) such that if paraoxonase-1 should influence serum HDL, it would be less effective in coronary cases. When examined as a function of the PON1 gene promoter polymorphism C-107T, highly significant differences (p<0.001) in HDL-cholesterol and apoA-I were observed between genotypes for controls, with high expresser alleles having highest HDL concentrations. This relationship was lost in cases with coronary disease. 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. The data are consistent with an impact of paraoxonase-1 on plasma concentrations of HDL, with detrimental modifications to the relationship in coronary cases.
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