The polymorphism of the human serum paraoxonase^†

Abstract

The activity of paraoxonase, the enzyme which hydrolyses paraoxon, 0,0-diethyl-0-4-nitrophenylphosphate, in human serum shows a genetically determined polymorphism with strong interethnic differences. The serum paraoxonase genotype has a significant influence on the paraoxon clearance. Individuals with high serum paraoxonase activity may be better protected against the toxic effects of parathion (0,0-diethyl-0-4-nitrophenylthiophosphate).In Caucasians the polymorphism is governed by two alleles. The first allele has a gene frequency p low of 0.67 to 0.78, and is manifested in both the form of a first homozygotic group with low activities and a second heterozygotic group with medium activities. About 50% of all Europeans belong to the low activity group. The second allele with a gene frequency q high of 0.22 to 0.33 is manifested in the second heterozygotic and a third homozygotic group with medium resp. high activities. The Hardy-Weinberg rule for a two allele model is valid for the distribution.The percentage of the low activity group decreases as one moves from Europe to Africa and Asia. In most of the Mongoloids and Negroids only 5 to 20% of the population can be included in the low activity group, which is not even demonstrable in Aborigines, Maoris, Tonga and some African and Indian (Central America) tribes. The validity of the Hardy-Weinberg rule for a two-or three-allele model must be rejected in non-Caucasians.