Paraoxonase (Pon1) Q192R polymorphism and serum Pon1 activity in diabetic patients on maintenance hemodialysis

Patients with diabetic nephropathy have an increased risk of coronary heart disease (CHD). Paraoxonase (Pon1) is a high-density lipoprotein- (HDL) associated enzyme that protects low-density lipoprotein from oxidation and also protects against atherosclerosis. We investigated the relationship of serum Pon1 activity, Pon1 Q192R polymorphism and HDL-C level to type 2 diabetes mellitus (DM) in patients on maintenance hemodialysis (HD). DM patients (n = 56, F/M = 17/39, aged 64.5 +/- 7.5 years) and non-DM patients (n = 89, F/M = 28/61, aged 62.7 +/- 8.3 years) under HD were included in this study. Salt-stimulated serum Pon1 activities were measured using paraoxon as a substrate. Pon1 Q192R polymorphism was detected by the mutagenically separated polymerase chain reaction. DM patients on HD had significantly lower HDL-C levels and serum Pon1 activities than non-DM patients on HD (657 +/- 277 vs. 763 +/- 257 IU/l, p < 0.01). The distribution of Pon1 Q 192R genotypes in all subjects did not differ from that predicted from the Hardy-Weinberg equilibrium. Serum Pon1 activities in both DM and non-DM patients on HD were regulated by Pon1 Q192R polymorphism: RR > QR > QQ. However, the reduced Pon1 activities in DM patients on HD were related to DM independent of the Pon1 genotype: reduced Pon1 activity was related to DM in RR carriers. Serum Pon1 activities were positively correlated with HDL-C levels. The association between HDL-C and DM in hemodialyzed patients was independent of Pon1 activity as assessed by an analysis of variance. But the relation between Pon1 activity and DM was modified by HDL-C levels: significantly when HDL-C was below 50 mg/dl, but not significantly when HDL-C was above 50 mg/dl. The results of a logistic regression analysis show that reduced serum Pon1 activities and low HDL-C levels were additively associated with DM. In conclusion, Pon1 status and HDL levels are independently associated with DM in patients on hemodialysis and may contribute to the increased risk of CHD in diabetic nephropathy.