|
Paraoxonase 1
Scientific background:
Summary: 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.
Gene: 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.
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.
Clinical signs: 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.
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.
Interpretation: The risk for diabetic retinopathy is 2.5 times increased in patients with LL-genotype. For artheriosklerotic disease different figures exist.
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.
Methodology:
|
research
test |
Method |
Hotspot sequencing |
| Turn-around time |
25 working days |
| Effort |
little |
| Specimen |
DNA |
| Quality assessment |
Internal quality control only |
| |
Only in the region of interest, known and new missense, nonsense and splice mutations can be detected. |
|
