Low serum paraoxonase: a risk factor for atherosclerotic disease?

Serum paraoxonase (PON1) hydrolyses organophosphate (OP) insecticides and n erve gases and is responsible for determining the selective toxicity of the se compounds in mammals. PON1 has two genetic polymorphisms giving rise to amino acid substitutions at position 55 and 192. The 192 polymorphism is th e major determinant of the PON1 activity polymorphism towards organophospha tes. However, the 55 polymorphism also modulates activity. PON1 also may be a determinant of resistance to the development of atherosclerosis by prote cting lipoproteins against oxidative modification perhaps by hydrolysing ph ospholipid-hydroperoxides. The PON1 polymorphisms are important in determin ing the capacity of high-density lipoprotein (HDL) to protect low-density l ipoprotein (LDL) against oxidative modification in vitro and this may expla in the relationship between the PON1 alleles and coronary heart disease in case-control studies. (C) 1999 Elsevier Science Ireland Ltd. All rights res erved.