Methodological constraints in interpreting serum paraoxonase-1 activity measurements: an example from a study in HIV-infected patients

We measured selected variables in 227 patients and in a control group of 409 participants. Serum PON1 esterase and lactonase activities were measured as the rates of hydrolysis of paraoxon and of 5-(thiobutyl)-butyrolactone, respectively. Oxidised LDL and MCP-1 concentrations were determined by enzyme-linked immunosorbent assay. High-density lipoproteins cholesterol, apolipoprotein A-I, and C-reactive protein concentrations were measured by standard automated methods.There were significant relationships between PON1 activity and several indices of oxidation and inflammation in control subjects and in infected patients. However, these relationships varied not only with disease status but also on the type of substrate used for PON1 measurement.The present study is a cautionary tale highlighting that results of clinical studies on PON1 may vary depending on the methods used as well as the disease studied. Until more specific methods using physiologically-akin substrates are developed for PON1 measurement, we suggest the simultaneous employment of at least two different substrates in order to improve the reliability of the results obtained.Paraoxonase-1 (PON1) is an enzyme with esterase and lactonase activities found in the circulation bound to high-density lipoproteins (HDL). Research into PON1 has increased exponentially over the past few years because many studies associate this enzyme with inflammation and cardiovascular disease. The physiological substrates of PON1 have not been completely delineated, but in vitro studies suggest that a key function is to degrade oxidised phospholipids in low-density lipoproteins (LDL) and HDL and, as such, has an antioxidant role [1]. PON1 attenuates the production of the monocyte chemoattractant protein-1 (MCP-1) in cultured endothelial cells. MCP-1 is a pro-inflammatory chemokine involved in the initial steps in the formation of the atheromatous plaque [2]. Previous studies from our group have shown that HIV-infected patients ha