Factors Associated with Paraoxonase Genotypes and Activity in a Diverse, Young, Healthy Population: The Coronary Artery Risk Development in Young Adults (CARDIA) Study (Lipids, Lipoproteins, And Cardiovascular Risk Factors‪)‬

Paraoxonase, a high-density lipoprotein particle-associated A-oxonase initially characterized by its ability to hydrolyze organophosphates including the insecticide paraoxon (1), has been implicated in cardiovascular disease pathogenesis (1-4). In experimental studies, paraoxonase may negate the damaging effects of organophosphates and oxidized lipids (5). Therefore, besides reverse cholesterol transport, high-density lipoprotein particles may prevent LDL oxidation through interaction with proteins such as paraoxonase (5). The paraoxonase family (PON1, PON2, and PON3) [5] is located on the long arm of human chromosome 7 (6). Two coding region polymorphisms (leucine to methionine substitution at codon position 55 [L55M] and glutamine to arginine substitution at codon position 192 [Q192R]) and 5 promoter region polymorphisms, such as C-108T, are known in the PON1 gene, whereas 2 common polymorphisms are known in the PON2 gene coding region (2). Among these, the Q192R and L55M polymorphisms are most strongly associated with paraoxon hydrolysis (3, 7, 8). The 55L and 192R allele frequencies are higher in blacks vs whites (9), and Chinese have the highest frequency of 55L (10). A recent metaanalysis found a significant association between Q192R and coronary heart disease, but no parallel association for L55M (11). In addition to the genetic polymorphisms, numerous environmental factors such as smoking, atherogenic diet, polyphenols, and alcohol may affect paraoxonase activity and its potential to alter the course of macrovascular disease (2).