engleski

Genetic polymorphism of the paraoxonase

Serum paraoxonase (PON1) recieved its name from the ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Recent studies suggest that PON1 acts as important quardian against cellular damage from toxic agents, such as organophosphates, oxidized lipids in the plasma low-density lipoproteins and against bacterial endotoxins. Human PON1 is 335-amino acids long glycoprotein and its gene is located on the long arm of chromosome 7, at q21-q22. PON1 circulates in blood as a component of high density lipoproteins. In human populations, serum paraoxonase exhibits a substrate dependent polymorphism. The molecular basis of PON1 polymorphism has been related to two amino acid substitutions, Arg for Gln at position 192 and Met for Leu at position 55, respectively. The highest activity against paraoxon has been assigned to the Arg variant and consequently a lower activity to the Gln one. PON1 activity is reduced in several groups of patients with increased risk for atherosclerosis such as individuals with hypercholesterolaemia, non-insulin-dependent diabetes, patients with vascular diseases and survivors of myocardial infarction. The frequency distribution of PON1 activity displayed bimodality with approximately comparable frequencies of the low- and high-activity alleles. According to the studies the European population generally exhibit 50 % homozygotes for a low PON activity isoform, 10 % homozygotes for the corresponding high-activity isoform, and 40 % heterozygotes. PON1 polymorphism can be investigated on DNA isolated from human leukocites by molecular biology methods such as PCR-RFLP or PCR-SSCP.

paraoxonase

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