Serum paraoxonase activity decreases in rheumatoid arthritis

Objective: To estimate the alterations of paraoxonase 1 (PON-1) and high-density lipoprotein (HDL) in rheumatoid arthritis (RA). Design and Methods: We investigated the serum enzyme activity and concentration of PON1 and their relationship With serum lipids, high-density lipoprotein (HDL) parameters, and acute phase reactants of serum amyloid A (SAA) and C-reactive protein (CRP) in patients with RA. Results: Serum paraoxonase (PON) activity was significantly decreased in RA patients (n = 64, 131 +/- 53 mumol/min/L) compared with healthy subjects (n = 155, 164 59) despite the absence of any difference in serum lipid levels between the two groups. This decrease of serum PON activity in RA patients was found in every genotype (Q/Q, Q/R, R/R) of PON1 at 192 Q/R. There was a different distribution in PON1 Q/R genotypes between RA patients and healthy subjects, and RA patients exhibited less (44%) positive PON1-Q than did the healthy subjects (66%). In a further investigation of age- and gender-matched subgroups of RA (n = 25) and healthy subjects (n = 25), not only serum PON activity, but also lecithin-cholesterol acyltransferase (LCAT) was found to be significantly decreased in RA patients (125 +/- 61 mumol/min/L, 63.2 +/- 17.2 nmol/ml/hr/37degreesC) than in healthy subjects (169 +/- 67, 74.7 +/- 19.5), respectively. PON1 and LCAT as well as HDL constituent apolipoprotein (apo) AI and apo All, were altered significantly in RA patients. Conclusions: Acute-phase HDL, which is remodeled structurally and functionally in RA, might be less anti-atherogenic due to the impairment of original HDL function. These alterations of HDL in RA patients may explain in part the reported increase in cardiovascular mortality in patients with RA. (C) 2003 Elsevier Science Inc. All rights reserved.