HDL3-related decreased serum paraoxonase (PON) activity in uremic patients: comparison with the PON1 allele polymorphism

Background: Patients with chronic renal failure on maintenance haemodialysis (HD) are at high risk of atherothrombotic events; an enhanced oxidant stress might have a major role. The decrease of human paraoxonase (PON1), an anti-oxidant high-density lipoprotein (HDL)-linked enzyme, is a possible mechanism for developing cardiovascular disease. To ascertain the causes of low PON1 in such patients, we investigated the contribution of both PON1 gene polymorphism and individual pattern of HDL. Methods: On 74 HD patients (47 M and 27 F) and on 92 healthy individuals (HS, 48 M and 44 F), we studied PON1 activity, PON1 genotype (55 and 192 PON1 allelic polymorphisms) and the lipid profile, including the HDL subtractions. Results: We observed in HD patients the following significant differences: (1) decreased median PON1 activity (73.5 vs. 110 U/1); (2) decreased mean HDL concentration (1.05 +/- 0.18 vs. 1.55 +/- 0.41 mmol/1); (3) decreased mean HDL3 concentration (0.79 +/- 0.21 vs. 1.28 +/- 0.24 mmol/1). Total HDL retained about 70% of serum activity, almost completely carried (95%) by the HDL3. Finally, PON1 activity remained significantly low in HD vs. HS after matching for the allelic polymorphism. Conclusions: The reduction of the HDL3, not the genetic PON1 polymorphism, seems the most important determinant of PON1 activity reduction in HD. (C) 2002 Published by Elsevier Science B.V.