The positive relationship of serum paraoxonase-1 activity with apolipoprotein E is abrogated in metabolic syndrome

High density lipoproteins (HDL) contain paraoxonase-1 (PON-1), which has strong anti-oxidative properties. Apolipoprotein E (apoE) may enhance PON-1 activity in vitro, but the extent to which PON-1 activity is determined by circulating apoE levels is unknown. Here we determined relationships of serum PON-1 activity with apoE in subjects without and with metabolic syndrome (MetS). We measured PON-1 activity (arylesterase activity), plasma apoE and serum amyloid A (SAA) in 93 subjects without and in 75 subjects with MetS (25 and 54 subjects with Type 2 diabetes mellitus (T2DM), respectively; p < 0.001). PON-1 activity was lower in MetS (p < 0.005) coinciding lower HDL cholesterol, apoA-I (p < 0.001)) and SAA levels (p < 0.01), whereas apoE was increased in relation to higher triglycerides (p < 0.01). In subjects without MetS, PON-1 activity was correlated positively with apoE (r = 0.376, p < 0.001), but this relationship was absent in MetS subjects (r = 0.085, p = 0.47). Multiple linear regression analysis showed that the relationship of PON-1 activity with apoE was different in subjects with MetS compared to subjects without MetS (β = -0.270, p = 0.014 for the interaction between apoE and MetS), independently from age, sex, T2DM, use of glucose lowering drugs, anti-hypertensives and the inverse relation with SAA levels (p = 0.008). Of the individual MetS components, apoE only interacted with low HDL-C on PON-1 activity (β = -0.175, p = 0.074). The relationship of apoE with PON-1 activity was neither modified by T2DM (p = 0.49), nor by SAA (p = 0.79). Higher apoE levels may confer higher PON-1 activity. The relationship of PON-I activity with total plasma apoE is apparently abrogated in MetS