San Francisco -- Paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL). The antioxidant properties of HDL are due largely to the ability of its associated PON1 to both remove lipid peroxides from low-density lipoproteins (LDL) and prevent the transformation of LDL into oxidized, atherogenic particles (OxLDL).
PON1 is named for its ability hydrolyze a synthetic compound known as paraoxon. Numerous genetic polymorphism have been identified within the PON1 locus that affect this function.
Perhaps the strongest is a single amino acid substitution that occurs at position 192. A glutamine (Q) at PON1 192 is associated with diminished enzymatic activity. At the same time, an arginine (R) in the same position results in a high-activity isoform. A second polymorphism of the PON1 gene results in an amino acid substitution at position 55. A smaller effect on activity against paraoxon has been noted at this locus with a leucine (L) at aa 55 being associated with greater activity than a methionine (M).
Increased PON1 isoenzymatic activity against paraoxon is opposite to its specificity and activity with respect to the hydrolysis of lipid peroxides. In fact, increased atherosclerosis has been associated with the high paraoxon hydrolysis activity PON1 R192 and L55 alleles. However, conflicting reports describe significantly diminished PON1 activity in patients with acute myocardial infarction (i.e., heart attack) and an increased risk of atherosclerotic symptoms in individuals with the low paraoxon activity PON1 192QQ genotype. Substantial inter-individual variation in PON1 activity has been described that may be independent of both the 55 and 192 polymorphisms.
While adult studies have demonstrated genetic regulation of PON1 activity, no investigations had been undertaken within the pediatric population. Accordingly, Michele Mietus-Snyder, MD of the Departments of Physiological Nursing and Pediatrics at the University of
Contact: Donna Krupa
American Physiological Society