Influence of PON1 Polymorphisms on the Association between Serum Paraoxonase 1 and Homocysteinemia in a General Population

Homocysteine (Hcy)-induced vascular impairment may be partially mediated by the production of Hcy thiolactone (HTL). This compound acylates side-chain lysine groups in proteins and alters protein structure and function. HTL is formed under conditions of high Hcy resulting from insufficient remethylation of Hcy to methionine; however, HTL is not a reliable marker of plasma total Hcy (tHcy). In healthy volunteers, it contributes only 0.14%–0.28% of tHcy, has a half-life of 1 h, and is below the detection limit in approximately one half of volunteers (1).Paraoxonase 1 (PON1) is a hydrolase associated with HDL that is thought to degrade lipid peroxides and HTL (2). Decreased PON1 activity has been associated with atherosclerosis (3). Hepatic expression of the PON1 gene is down-regulated in hyperhomocysteinemic mice (4); it is plausible, therefore, that the proatherogenic effects of Hcy may involve diminished serum PON1 activity, leading to impaired antioxidant function and …