Genetics of paraoxonase.

Area of Science:

• Biochemistry
• Human Genetics
• Population Genetics

Background:

• Paraoxonase activity is crucial for detoxifying organophosphates.
• Understanding the genetic control of paraoxonase is important for health and toxicology.
• Previous studies suggested genetic variability in paraoxonase activity.

Purpose of the Study:

• To investigate the genetic basis of paraoxonase activity in a large Danish family cohort.
• To determine the inheritance pattern and gene frequency of paraoxonase phenotypes.
• To refine methods for classifying paraoxonase activity levels.

Main Methods:

• Analysis of paraoxonase activity in 1664 parents, 3169 children, and 699 grandparents.
• Utilized a micro-autoanalyzer with a two-stage pH testing method (pH 7.5 and pH 10) for improved discrimination.
• Phenotypic classification into 'low' and 'high' activity groups.

Main Results:

• The family material supported a model of autosomal recessive inheritance for the low paraoxonase phenotype.
• The estimated gene frequency for the low phenotype (plow) was 0.726.
• Out of 5532 individuals analyzed, 5 exhibited an almost complete lack of paraoxonase activity.

Conclusions:

• Paraoxonase activity is primarily controlled by an autosomal recessive gene.
• The developed two-stage pH testing method provides unequivocal classification of paraoxonase phenotypes.
• This study provides valuable data on the population genetics of paraoxonase in a Danish cohort.