Methods in Genetics and Clinical Interpretation Determination of Paraoxonase 1 Status Without the Use of Toxic Organophosphate Substrates

Paraoxonase 1 (PON1) is a member of a tandem 3-gene family localized on human chromosome 7q21-22.1 High-density lipoprotein-associated PON12,3 and PON34,5 are synthesized primarily in the liver, whereas PON2 is ubiquitously expressed.1 PON1 was initially characterized and named for its ability to hydrolyze paraoxon, the toxic oxon metabolite of parathion.6 Although Aldridge6 proposed in 1953 that serum paraoxonase (POase) and arylesterase (AREase) activities were carried out by the same enzyme, controversy about 1 versus 2 enzymes persisted for many years, resulting in a reclassification of POase/ AREase from EC 3.1.1.2 to EC 3.1.8.1 for PON1 as an example of an organophosphorus (OP) hydrolase.7 The controversy was finally settled when Sorenson et al8 demonstrated both activities in recombinant PON1. However, the revised nomenclature remains in place. Early studies of plasma PON1 found a large variability of POase activity among different species and in different tissues.6 Serum POase activity distribution studies in human populations revealed an activity polymorphism of high versus low POase activity. Studies on the polymorphic distribution of PON1 in human populations using a variety of different assays revealed bi or trimodal distributions of plasma POase activity (reviewed in Ref.9).