Main determinants of PON1 activity in hemodialysis patients

Cardiovascular diseases are the major cause of morbidity and mortality in hemodialysis (HD) patients. These patients present reduced paraoxonase 1 (PON1) activity that depends on genetic and non-genetic factors; however, how these factors influence PON1 activity in HD patients is poorly clarified. Our aim was to evaluate the influence of two polymorphisms and non-genetic factors on PON1 activity in HD patients.

We evaluated 183 HD patients under recombinant human erythropoietin (rhEPO) treatment and 22 healthy individuals. The lipid profile [total cholesterol, triglycerides, HDL-c, LDL-c, apolipoprotein (Apo) A-I, Apo B, lipoprotein(a) and oxidized low-density lipoprotein (Ox-LDL)], inflammatory markers [adiponectin, interleukin-6 (IL-6) and C-reactive protein (CRP)], PON1 activity and PON1 gene polymorphisms (L55M and Q192R) were evaluated.

HD patients presented higher levels of IL-6, CRP and Ox-LDL/LDL-c, and lower PON1 activity, total cholesterol, HDL-c, LDL-c, Apo A and Apo B; the most frequent genotype was heterozygosity for L55M polymorphism and homozygosity for the Q allele, the more frequent genotype of Q192R polymorphism. Multiple regression analysis identified heterozygosity and homozygosity for L55M and Q192R polymorphisms, very low-density lipoproteins, LDL-c, Apo A and CRP levels, time on dialysis and rhEPO dose, as the independent variables significantly associated with PON1 activity. The associations with CRP, rhEPO and time on dialysis were negative.

Our results show that the reduced PON1 activity in HD patients who are not under statin therapy is strongly associated with inflammation, longer time on dialysis and high rhEPO doses, suggesting that the reduction in PON1 activity may worsen the prognosis of these patients.