Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy

Human serum paraoxonase I (PON 1) is located on high-density lipoprotein an d has been implicated in the detoxification of organophosphates, and possib ly in the prevention of lipid peroxidation of low-density lipoprotein. PON 1 has two genetic polymorphisms, both due to amino acid substitutions: one involving glutamine (Q genotype) and arginine (R genotype) at position 192, and the other involving leucine (L genotype) and methionine (M genotype) a t position 55. We investigated the effects of these polymorphisms, and of a polymorphism of the PON 2 gene at position 310(Cys/Ser; C and S genotypes respectively), on serum PON 1 activity and concentration, plasma lipids and lipoproteins and glycaemic control in 93 individuals with type II diabetes with no complications and in 101 individuals with type II diabetes with re tinopathy. Serum PON 1 activity in the group with no complications [median 164.1 nmol . min(-1) . ml(-1) (range 8.0-467.8)] was significantly higher t han in the group with retinopathy [113.4 nmol . min(-1) . ml(-1) (3.0-414.6 )] (P < 0.001), but the serum PON 1 concentration was not different between the groups. The gene frequencies of the PON 1-55 and PON 1-192 polymorphis ms and of the PON 2-310 polymorphism were not different between the study p opulations. The PON 1-55 and PON 1-192 polymorphisms affected PON 1 activit y in the way described in a previous study of a control group and subjects with type II diabetes. The PON 2-310 polymorphism also significantly affect ed serum PON 1. PON 1 activity was significantly higher in individuals with the PON 2-310 CC genotype in both groups with type II diabetes, and the PO N 1 concentration was significantly higher in PON 2-310 CC homozygotes with no complications than in the group with retinopathy. Neither the PON 1-55 nor the PON 1-192 polymorphism was correlated with the serum lipid or lipop rotein concentration in either group. In the group with retinopathy (but no t the group with no complications), all three PON polymorphisms were correl ated with glycaemic control, which was worse for the PON 1-55 genotypes in the order MM > LM > LL (P = 0.0032), for the PON 1-192 genotypes in the ord er RR,QR > QQ (P = 0.01 I) and for the PON 2-310 genotypes in the order CC > CS > SS (P = 0.010). Low serum PON 1 activity in retinopathy may be relat ed to an increased tendency for lipid peroxidation. Our findings thus raise the possibility that, in retinopathy, the PON 2 gene may influence PON 1, and that an inter-relationship between the PON 1 and PON 2 genes may influe nce glycaemic control in subjects with type II diabetes complicated by reti nopathy.