Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Paraoxonase 1

The biochemical function of the enzyme paraxonase is radical removal. Mutations of this gene seem to play a role in the pathogenesis of arteriosclerosis and diabetic retinopathy.

Epidemiology

The allel frequencies for M and L-allel at position 54 and for Q and R-allel at position are 40%, 60% and 65%, 35% respectively. The frequency of M-allel increases in Europe from North to South.

Gene Structure

The gene known with the short name PON1 is about 27kb in size. It is located on chromosome 7 (7q21.3). It consists of 9 exons.

Phenotype

The mutations (M54L, Q191R) result in reduced plasma activity in spite of normal plasma concentrations of this enzyme. As a consequence there is a higher risk of arteriosklerotic complications especially in states where a higher production rate of radicals can be expected i.e. in diabetes.

Pathology

The translational product of the gene is an antioxidative enzyme that is carried by the HDL particles. Its function is the removal of oxidative radicals and this way it has protective properties agains artherosclerosis. There was a higher incidence of arteriosclerotic complications and diabetic retinopathy observed in patients where a mutation of this gene leads reduced plasmatic activity.

Test Strategy

The genetic test should not be considered before clinical manifestation of diabetes. The test can help to define the need and the schedule of diagnostic an therapeutic procedures. This is specially important in families with increased risk.

Interpretation

The risk for diabetic retinopathy is 2.5 times increased in patients with LL-genotype. For artheriosklerotic disease different figures exist.

Genetests:

Research Method Target mutation analysis
Turnaround 20
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25
Specimen type genomic DNA

Related Diseases:

Diabetic retinopathy
PON1
VEGFA
Arteriosclerosis
APOB
APOE
HABP2
LDLR
LPA
MTHFR
PON1
SLC3A1

References:

1.

Mackness B et al. (2000) Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy.

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2.

Deakin S et al. (2002) Paraoxonase-1 L55M polymorphism is associated with an abnormal oral glucose tolerance test and differentiates high risk coronary disease families.

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3.

Kao YL et al. (1998) A variant of paraoxonase (PON1) gene is associated with diabetic retinopathy in IDDM.

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Update: Sept. 26, 2018