Estimation of the Distribution of a Genetically Determined Enzyme Polymorphism by a Stochastical Outside Criterion

Toxicological & Environmental Chemistry

1988

111

Human serum contains EDTA-sensitive (Ca ++ -dependent) and EDTA-stable (albumin) paraoxonases which hydrolyse paraoxon, 0,0-diethyl,0-4-nitrophenyl phosphate.In Caucasians the EDTA-sensitive enzyme shows a genetically determined polymorphism which is governed by two alleles. In typical Mongoloid or Negro populations this polymorphism is expressed to a lesser degree, and in a few samples (e.g. Aborigines) it cannot be observed at all. The distribution of the activity of the EDTAstable (albumin) paraoxonase is unimodal.Many authors supposed that paraoxonase is an arylesterase (EC 3.1.1.2) which means that it is also able to hydrolyse phenylacetate or β-naphthylacetate. New investigations have shown that the human serum fractions splitting paraoxon can be separated from those hydrolysing phenylacetate and related substrates.The polymorphism of the EDTA-sensitive human serum paraoxonase can be applied to investigations concerning specificity. From this it becomes evident that this enzyme is rather specific. Already slight changes of the paraoxon molecule lead to a decrease of activity. On the other hand the enzyme seems to hydrolyse also phosphonic acid esters and 4-nitrophenylacetate in the same way like paraoxon (polymorphism).There is a linkage relationship of paraoxonase with cystic fibrosis and DNA markers. According to these results the (EDTA-sensitive) paraoxonase locus is on the human chromosome 7.A high serum paraoxonase level actually protects serum cholinesterase (EC 3.1.1.8) and has to be considered in biological monitoring of workers exposed to parathion.

Section: Methodsmentioning

confidence: 99%

Section: Statistical Analysis With the Computer Program Genitermentioning

confidence: 99%

The human serum paraoxonase—Polymorphism and specificity

Mallinckrodt¹,

Toxicological & Environmental Chemistry

1988

111

“…Hommel 22 described the mathematical model for separation of a population into groups according to enzyme activities assuming a two-allele model. On the basis of this model the computer program GENITER 23 was developed which is suitable for the iteration of a two-or three-allele model.…”

Section: Methodsmentioning

confidence: 99%

The polymorphism of the human serum paraoxonase^†

Mallinckrodt

Toxicological & Environmental Chemistry

1987

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.

“…Hommel (1978) described the mathematical model for separation of a population into groups according to enzyme activities assuming a two-allele model. On the basis of this model the computer program GENITER (Hommel et al, 1980) was developed, which is suitable for the iteration of a two-or threeallele model.…”

Section: Methodsmentioning

confidence: 99%

A study of the polymorphism and ethnic distribution differences of human serum paraoxonase

Mallinckrodt

American J Phys Anthropol

Duhme

et al. 1983

Self Cite

The enzyme serum paraoxonase shows a polymorphism in Europeans which is governed by two alleles. The first allele has a gene frequency plow of 0.716-0.777, and is manifested as a low activity group in homozygotes. More than 50% of all European test subjects can be included in this group. A second allele with a gene frequency qhigh of 0.223-0.284 was found in typical European distributions and is manifested in both the form of a second heterozygotic and a third homozygotic group with high activities. The Hardy-Weinberg rule for a two-allele model is valid for the distribution. The gene frequency plow of the first allele decreases as one moves from Europe in the direction of Africa and Asia. In typical Mongoloid and Negroid collectives, less than 10% of the population can be included in the low-activity group, a group which is not even demonstrable in the Aborigines of Australia. The serum paraoxonase of the Aborigine population shows unimodal distribution. The validity of the Hardy-Weinberg rule for a three-allele model must be rejected in all examined collectives. Human serum paraoxonase shows neither age-related changes in activity nor sex-dependent activity differences.