Polymorphisms of human paraoxonase 1 gene (PON1) and susceptibility to diabetic nephropathy in Type I diabetes mellitus

Aims/hypothesis. Oxidative stress is a putative mechanism in the developmen t of diabetic nephropathy. Paraoxonase gene 1 is an HDL-bound enzyme that p rotects tissues against oxidative damage. Three common polymorphisms of par aoxonase gene 1, T-107C in the promoter, Leu54Met and Gln192Arg, that modif y paraoxonase activity have been associated with cardiovascular disease. Th is study aimed to find whether these polymorphisms also contribute to the d evelopment of diabetic nephropathy. Methods. The association between diabetic nephropathy and these three polym orphisms was examined in a case-control study. For this purpose, genomic DN A was collected from 188 patients with Type I (insulin-dependent) diabetes mellitus and diabetic nephropathy and from 179 unrelated patients with Type I diabetes but without diabetic nephropathy despite the duration of diabet es of 15 or more years. Results. The genotype and allele frequencies for each of the three polymorp hisms (T-107C, Leu54Met and Gln192Arg) were similar in cases and control su bjects. Conclusion/interpretation. The three polymorphisms in paraoxonase gene 1 th at have been associated with serum levels of paraoxonase are not associated with diabetic nephropathy. We show that this genetically determined compon ent of the antioxidant capacity of HDL does not play a critical part in the development of diabetic nephropathy.