Effects of paraoxonase 1 L/M 55 and Q/R 192 polymorphisms on enzyme activities of paraoxonase 1 and antioxidant enzymes and lipid levels in patients with type 2 diabetes mellitus

Paraoxonase 1 (PON 1), is a HDL- associated enzyme with antioxidant function protecting LDL from oxidation. PON 1 has two aminoacid polymorphisms in coding region; one Leu-Met at position 55 (L/M55) and the other Glu-Arg at position 192 (Q/R 192). L/M 55 ve Q/R 192 polymorphisms modulates paraoxonase activity and antioxidant function of the enzyme. PON 1 activity decreases in diabetes mellitus and an association between this reduction and development of diabetic complications has been indicated.In the present study, distribution of PON 1 L/M 55 and Q/R 192 polymorphisms and the effect of these polymorphisms on the activities of PON 1, SOD, CAT, GSH-Px, lipid peroxidation and lipid profile in 102 non-diabetic healthy subjects (57 female/45 male; control group) and 200 patients with type 2 diabetes mellitus (115 female/85 male; DM group) were examined.PON 1 L/M 55 ve Q/R 192 genotypes were determined by PCR, RFLP and agarose gel electrophoresis techniques. Genotype distributions and allel frequencies for both polymorhisms were not significantly different between controls and DM group (p>0.05). Serum PON 1 paraoxonase activity was lower in DM group than in controls but not statistically significant (p>0.05). In both groups, the highest paraoxonase activities were detected in LL and RR genotypes, intermediate activities in LM and QR genotypes, and the lowest activities in MM and QQ genotypes.Activities of erythrocyte GSH-Px and CAT were significantly lower (p<0.01 and p<0.05, respectively), while decrease in SOD activity was not statistically significant (p>0.05), in DM group than in control group. Levels of MDA, an indicator of lipid peroxidation were significantly higher in DM group (p<0.001).No significant difference in HDL-cholesterol levels was detected between both groups but LDL-cholesterol, total cholesterol and triglyceride levels were significantly higher in DM group (p<0.001). Presence of R and M allels in control group and presence of Q and M alles in DM group accompanied with higher atherogenic lipid profile.In conclusion, data obtained from the present study indicates that PON 1 L/M 55 ve Q/R 192 polymorphisms cause significant alterations in paraoxonase activity of the enzyme, however it is hard to correlate these polymorphisms and risk for type 2 diabetes mellitus and oxidant-antioxidant alterations observed in diabetes, For a better understanding of the role of PON 1 in type 2 diabetes mellitus, in addition to polymorphisms in coding region, 5 polymorphisms in promotor region which are also related to antioxidant function of the enzyme and PON 2 and PON 3, two other members of PON family, also should be investigated.