Paraoxonase 1 Polymorphisms Research Articles

The human serum paraoxonase—Polymorphism and specificity

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 EDTA‐stable (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.

The interethnic differences of the human serum paraoxonase polymorphism analysed by a quantitative and a qualitative method

The polymorphism of the human serum paraoxonase1 was analyzed by two distinguished methods in six different ethnic groups (Caucasians, Mongoloids, Negroids), using (1) the Computer Method2 and (2) the Carro‐Ciampi Method3‘4. Analysis of the response of the enzyme activities to salts resulting in low and high activity ratios. Comparison of the results: In Caucasians we distinguished three phenotypes by the Computer method. The polymorphism was governed by two alleles. The Hardy‐Weinberg rule for a two‐allele model was valid. Individuals belonging to the homozygotic group with low activity had a low activity ratio (Carro‐Ciampi method). With both methods a frequency between 57% and 61% was observed for this group. Individuals with medium and high activity had a high activity ratio. In Negroids and Mongoloids samples we found (by the Computer method) a low activity group (Ghanaians 9.6%, Jamaicans 13.6%, Indonesians 6.7%, Koreans 19.6%). The Hardy‐Weinberg rule for a two‐ or three‐allele model was not valid. Individuals belonging to the low activity group had a low activity ratio, all individuals with higher activity a high activity ratio (Carro‐Ciampi method). Our results suggest that the members of the low activity group in the three races are homozygote for an identical allele.

Ecogenetic studies in Atacameño Indians.

Aldehyde dehydrogenase deficiency, N-acetyltransferase variation and the polymorphisms of alpha 1-antitrypsin, serum cholinesterase, paraoxonase, and delta-aminolevulinic acid dehydratase were investigated in 180 Atacameño Indians from the North of Chile. The genetic predisposition of these individuals for possible atypical reactions against environmental agents and drugs, as well as general implications of these findings, are discussed.

Genetisch determinierter Polymorphismus der menschlichen Serum-Paraoxonase (EC 3.1.1.2)

Menschliches Serum besitzt ein Enzym (augenblickliche Bezeichnung Arylesterase, Paraoxonase, EC 3.1.1.2), das aus Paraoxon (0,0-Diathyl-0-(p-nitrophenyl)-phosphat)p-Nitrophenol abspaltet. Dieses weist einen Polymorphismus auf, der, wie die Untersuchung von 35 Familien mit 52 Kindern zeigte, wahrscheinlich genetisch determiniert ist und einem einfachen 2-Allele-Modell folgt.