THU0079 HDL, IGG anti-HDL Antibodies and PON1 Axis in Rheumatoid Arthritis Patients: A New Target for CV Disease

BackgroundHigh Density Lipoproteins (HDL) seem to develop cardioprotective functions beyond the reverse cholesterol transport, thus pointing to their antioxidant activity as a crucial player. Paraoxonase 1 (PON1) is a HDL-associated antioxidant enzyme which has an important role in avoiding lipid oxidization. Although genetic polymorphisms are known to modulate PON1 activity, its involvement in cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) is controversial, suggesting that other factors may modulate its function.Objectivessince anti-HDL antibodies have been related to an impaired lipid profile and CVD in RA, we aimed to evaluate the associations between PON1 activity, anti-HDL antibodies and CVD in RA according to PON1 rs662 genetic variants.Methodsserum PON1 activity, using paraoxon as substrate, and IgG anti-HDL antibodies were quantified in 212 RA patients and 110 healthy controls (HC). The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologic-naïve RA patients was prospectively followed for three months.ResultsPON1 activity was decreased in RA compared to HC (p=0.005). PON1 rs662 variants influenced serum PON1 activity in both groups, QQ homozygotes exhibiting the lowest activity. Distribution of genotypes did not differ between groups (p=0.215) and Hardy-Weinberg equilibrium was observed in both populations. Interestingly, PON1 activity was not associated with disease activity, ESR or CRP. A multivariate ANOVA analysis confirmed an independent role of both rs662 (p