Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns Study.

Objective: Paraoxonase-1 (PON1) is suggested to have a role in the antioxidant activity of high-density lipoprotein (HDL). PON1 activity levels are strongly genetically determined by the rs662 polymorphism (PON1 Q192R). To clarify the role of PON1 in lipoprotein oxidation at the population level, we examined the relations between PON1 activity, the rs662 polymorphism and oxidized lipoprotein lipids in young adults.

Methods: A population-based cross-sectional study of 1895 Finnish adults ages 24-39 years (872 males and 1023 females). PON1 activity was determined with paraoxon as the substrate. Analysis of oxidized lipids in isolated HDL (oxHDLlipids) and low-density lipoprotein (oxLDLlipids) was based on the determination of conjugated dienes. Oxidized LDL was also measured with a method based on antibodies against oxidized Apo-B (oxLDLprot). Serum lipids and apolipoproteins were measured. Genotyping was performed with the Illumina Bead Chip (Human 670 K).

Results: In multivariable models, PON1 activity associated inversely with oxLDLlipids (p = 0.0001, semi-partial R(2) = 0.09%), but it was not associated with oxHDLlipids (p = 0.93). There was a borderline significant association between PON1 activity and oxLDLprot (p = 0.08). PON1 rs662 polymorphism was strongly associated with PON1 activity (P-value<0.0001), but not with oxidized lipoprotein lipids and oxLDLprot.

Conclusion: Higher PON1 activity is associated with decreased oxLDLlipids levels, but not with oxHDLlipids in a population of young Finnish adults. These findings support the suggestion that PON1 activity may have a role in the oxidation of LDL lipids. There is a strong association between PON1 rs662 polymorphism and PON1 activity, but PON1 rs662 polymorphism is not associated with oxidized lipoprotein lipids and oxLDLprot.