Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes

Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis. We detected 3 polym orphisms of the PON1 gene and investigated PON1 enzyme activities as paraox onase (PON), arylesterase (ARYL) and diazoxonase (DIAZ), and serum PON1 con centration in 106 patients with type 2 diabetes and 161 control subjects. A ll 3 enzyme activities and specific activities of PON1 in diabetic patients were significantly lower than those in controls, while there was no differ ence in serum PON1 concentration between the patient and control groups. Th e specific activities of PON, ARYL, and DIAZ in patients were 6.82 +/- 3.14 nmol.min(-1) U-1 (mean +/- SD, U; unit for serum PON1 concentration), 4.77 +/- 0.17 mu mol min(-1) U-1, and 193 +/- 92 nmol min(-1).U-1, respectively , whereas those in controls were 9.33 +/- 3.92 nmol.min(-1).U-1, 5.36 +/- 0 .14 mu mol min(-1).U-1, and 242 +/- 103 nmol.min(-1) U-1, respectively. The re was no significant difference in the allelic frequencies of -108C/T, 55L /M, or 192Q/R between the patient and control groups. When each enzyme acti vity was compared between the patient and control groups in each genotype s ubgroup, all activities were lower in the patient group. The PON and ARYL a ctivities were lower in patients with retinopathy or nephropathy than in th ose without such complications, and the ARYL activity was also lower in pat ients with neuropathy. In conclusion, all specific enzyme activities of PON 1 were lower in patients with type 2 diabetes independent of the -108C/T, 5 5L/M, or 192Q/R polymorphism, and this impaired PON1 function may he involv ed in development of diabetic microangiopathy. Copyright (C) 2000 by W.B. S aunders Company.