PON1 gene and Antioxidant Needs
PON1 gene in humans is located on the long arm of chromosome 7.
This gene was the first discovered gene of the paraoxonase multigene family along with the PON2 and PON3 genes.
The PON1 gene codes for the enzyme serum paraoxonase/arylesterase 1 or PON1 that has esterase and paraoxonase activity.
The PON1 enzyme is composed of 354 amino acids and is synthesized by the liver.
PON1 associates itself with High-Density Lipoprotein (HDL) in the circulation.
The PON1 gene shows many polymorphisms in the coding and promoting regions.
Polymorphisms in the PON1 gene have an association with coronary artery disease and diabetic retinopathy.
PON1 association with antioxidant needs
PON1 plays a major role in oxidative stress and inflammatory response by virtue of its association with HDL cholesterol in the body.
HDL facilitates the secretion of the PON1 enzyme, which in turn prevents the oxidation of HDL and stimulates cholesterol efflux from the cells.
These together offer an atheroprotective function to HDL.
What are antioxidants?
As the name goes, these substances and compounds inhibit oxidation in the body.
Antioxidants are natural compounds that help neutralize free radicals in our bodies.
Free radicals are substances whose elevated levels can be harmful to the body.
The elevated levels have an association with diseases like cancer, heart disease, diabetes, and aging.
What is the function of antioxidants?
Our body cells constantly produce free radicals as a reaction to internal body and environmental pressures and stresses.
The cells in our body are responsible for the production of these free radicals.
These are unstable molecules, and thus can cause slow cell damage.
Since these free radicals are reactive oxygen species, the antioxidants naturally counter them.
Antioxidants are neutralizers of these free radicals and can be obtained by consuming foods that are rich in them.
In individuals who are healthy and disease-free, there is a balance of antioxidants that counter the effects of the reactive free radicals.
What’s the genetic link?
|rs854560||T||Beneficial of antioxidant needs|
|rs662||C||Risk of antioxidant needs|
SNP rs854560 is a polymorphism that is present on the PON1 gene associated with antioxidant needs.
The variants of this SNP affect levels of the PON1 enzyme and have an association with coronary diseases and diabetes. The T allele is the more favorable form of the SNP and codes for methionine, which leads too elevated levels of paraoxonase.
This is beneficial to the body.
However, the A allele codes for leucine; this leads to reduced paraoxonase activity, which is harmful to the body.
|rs854560||AA||2x Higher risk of Coronary Heart Disease and Diabetic retinopathy|
|rs854560||AT||2x Higher risk of Coronary Heart Disease and Diabetic retinopathy|
|rs854560||TT||1.8x Higher risk of Coronary Heart Disease and Diabetic retinopathy.|
SNP rs662, also called as Q192R is a polymorphism of the PON1 gene.
The C allele codes for arginine, whereas the less common T allele codes for glutamine.
The presence of the TT allele can imply lower or decreased levels of PON1 enzyme activity. Higher the PON1 enzyme activity, the lower is the risk for heart disease.
The TT allele also increases the risk of coronary heart disease by 2.3x and also increased the risk of vascular dementia, kidney disease, ischaemic heart disease, and male infertility.
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