Paraoxonase activity and paraoxonase 1 gene polymorphism in patients with uremia.

Abstract

Patients on hemodialysis (HD) show an increased risk for developing atherothrombotic events. The oxidative modification of low density lipoproteins (LDL) play an important role in the pathogenesis of atherosclerosis. In patients with uremia (chronic renal failure and HD), the increased oxidative stress induces oxidative modification of LDL. High density lipoproteins (HDL) exhibit a double antiatherogenic role, removing both lipid peroxides from LDL and cholesterol from tissues or vascular wall. Paraoxonase 1 (PON1) is one of three enzymes shown to prevent the formation of oxidized LDL. PON1 activity is modulated by its genetic polymorphism and by non-genetic factors, such as diet, smoking, acute phase reactants, and hormones. PON1 activity has been found to be significantly decreased in uremia. The present study aimed to verify the possibility that this reduced activity could be caused by a different PON1 gene polymorphism between patients on HD and healthy subjects, but this was not the case. The main cause may be identified in the different distribution of HDL subspecies, rather than in the different PON1 allele distribution between healthy subjects and patients with uremia.