Review: The role of paraoxonase in cardiovascular diseases

Paraoxonase (PON) is a group of proteins present in three forms (PON1, PON2, PON3) encoded by genes PON1, PON2, and PON3. PON1 and PON3 are plasma enzymes, structurally and functionally related to HDL, while PON2 is characterized by an intracellular location. Many polymorphisms of PON have been observed. The most widely and accurately described is the single nucleotide polymorphism, which impacts the conversion of glutamine (Q) to arginine (R) and has the effect of altering the hydrolytic activity of the PON1 form. Each PON form plays an important role in the human body, and they exhibit antioxidant, antiatherosclerotic, and anti-inflammatory influences. The PON family inhibits LDL oxidative modification and suppresses the differentiation of monocytes into macrophages, which is the first stage in the development of atherosclerosis. Furthermore, PON1 prevents the accumulation of oxidized LDL and stimulates cholesterol efflux from macrophages. Establishing these functions has led researchers to study the relationship between PON family and lipids in healthy subjects and in patients with diagnosed cardiovascular diseases. There is a certain relation between PON1 polymorphism and HDL and LDL particles. The PON1192RR genotype is associated with lower HDL levels and higher LDL levels. Lower concentrations of LDL in people with genotype PON155LL have been noted. These dependencies have been observed among healthy people, but the relation disappears in patients with cardiovascular diseases.