PLASMA PARAOXONASE POLYMORPHISM - A NEW ENZYME ASSAY, POPULATION, FAMILY, BIOCHEMICAL, AND LINKAGE STUDIES

Abstract

Plasma paraxonase hydrolyzes paraoxon, the principal metabolite of the insecticide parathion. A genetic polymorphism for enzyme activity was previously demonstrated. A new assay is described based on the differential inhibition by EDTA of plasma paraoxonase from persons with the high-activity allele (PX*H) that suggests a trimodality of activity levels in population studies. The gene frequency of the low activity allele (PX*L) in 531 Seattle [Washington, USA] blood donors of European origin was .7207. Family studies were consistent with codominant autosomal inheritance of 2 alleles, PX*L (low) and PX*H) (high), coding for products with different activity levels. Biochemical measurements of sera from presumed homozygotes for the 2 different alleles revealed minor physicochemical differences suggestive of a structural difference between the allelic products. No evidence for linkage of the paraoxonase locus with any of 19 polymorphic markers would be detected.