PARAOXONASE 1 Gene Polymorphism Relationship with Type 2 Diabetes Mellitus

Background: Human serum paraoxonase1 (PON1) an antioxidant enzyme closely associated with high density lipoprotein (HDL) has been implicated in the prevention of low density lipoprotein (LDL) oxidation and these may provide HDL-associated protection against atherosclerosis. The aim of this study is to investigate PON1 activity and its gene polymorphism in type 2 diabetes mellitus and its potential significance in the occurrence of diabetic complications. Patients and Methods: This study includes 60 subjects divided into: Twenty healthy subjects as a control (group I), Twenty diabetic patients without vascular complications (group II), and Twenty diabetic patients with vascular complications (group III). Laboratory investigations included: estimation of PON1 enzymatic activity by hydrolysis of paraoxon and PON1gene polymorphism by polymerase chain reaction (PCR) followed by polymorphism specific restriction enzyme digestion, other investigations included fasting and post prandial plasma glucose (FPG and PPPG), glycosylated hemoglobin (HbA1c) and lipid profile. Results : It revealed that PON1 activity was significantly lower in diabetics than control (p<0.001) and is lower in group III (183.6 +/- 52.01) than group II (230.05 +/- 59.75). PON1 was negatively correlated to HbA1c(r = -0.540, P<0.001). Gene and allele frequencies was significantly different in diabetics than control at 192 polymorphism (X-2 = 7.645, P<0.05) but not at 55 polymorphism with QQ higher in diabetics (77.5\%) and RR higher in controls (25\%). In both control and diabetics QQ and MM genotypes have the lowest activity of PON1 and RR and LL genotypes have the highest activity and QR and LM genotypes have intermediate activity, HbA1c was highest in QQ and MM genotypes, intermediate in QR and LM genotypes and lowest in RR and LL genotypes. The allelic frequency of Q and M genotypes were higher in group III than in group II and R and L genotypes were lower in group III than in group II. Conclusion: Paraoxonase activity is affected by PON1 genetic variability in type2 diabetic patients. The PON1 QQ and MM genotypes are associated with lower PON1 activity than RR and LL genotypes. In type 2 diabetic patients the QQ and MM genotypes are more common and associated with poor glucose control mainly in diabetic patients with vascular complication which suggest their essential roles in occurrence of diabetic vascular complications. {[}Elatar N., Swelam E.E1, Hamed E; Elnahal S, and Mostafa E. PARAOXONASE 1 Gene Polymorphism Relationship with Type 2 Diabetes Mellitus. Life Sci J 2012;9(3):1742-1751] (ISSN: 1097-8135). http://www.lifesciencesite.com.253