Lipid peroxidation is increased in paraoxonase L55 homozygotes compared with M-allele carriers

Human serum paraoxonase (PON) is an antioxidative enzyme, which circulates on high-density lipoproteins and appears to use oxidized phospholipids as physiological substrates. PON M/L55 substitution changes the ability of PON to prevent lipid oxidation. Urinary 8-iso-PGF2α (one of F2-isoprostanes) may represent a non-invasive in vivo index of free radical generation and we propose that PON might influence the biosynthesis of 8-iso-PGF2α in the vasculature. We studied the urinary excretion of 8-iso-PGF2α and related it to PON M/L55 genotypes in patients with type 2 diabetes mellitus (n = 55) and non-diabetic control subjects (n = 55). Urinary 8-iso-PGF2α was determined by competitive ELISA and the PON genotype by a PCR based restriction enzyme digestion method. LL homozygotes were compared to M-allele carriers (ML heterozygotes and MM homozygotes). The urinary excretion of 8-iso-PGF2α among non-diabetic non-smoking LL homozygotes was 3995.5 ± 3352.8 ng/24-hour and among M-allele carriers 1689.8 ± 1051.3 ng/...