Our data support the view that there is no association between the early changes of atherosclerosis as defined by carotid IMT and variation in codon 192 of PON 1.
Our findings thus raise the possibility that PON1 may be of importance in both the genetic and acquired predisposition to premature atherosclerosis and neuropathy in diabetes.
Thus PON1 may be a determinant of resistance to the development of atherosclerosis by protecting lipoproteins against oxidative modification, perhaps by hydrolysing phospholipid and cholesteryl-ester hydroperoxides.
PON1 also may be a determinant of resistance to the development of atherosclerosis by protecting lipoproteins against oxidative modification perhaps by hydrolysing phospholipid-hydroperoxides.
This functional relationship could explain the reported associations between common variation in the PON1 gene and phenotypes related to atherosclerosis and lipoprotein metabolism.
This functional relationship could explain the reported associations between common variation in the PON1 gene--at codons 55 and 192--and phenotypes related to atherosclerosis and lipoprotein metabolism.
Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis.
The observed interaction with type 2 diabetes, however, is supporting the hypothesis that the effect of the PON1 192 Arg allele on atherosclerosis is modulated by other risk factors like diabetes.
The decrease in PON1 enzyme activity in hemodialysis patients may modify a susceptibility to oxidization of LDL, which contributes to an acceleration of atherosclerosis.
We describe experimental conditions that permit the simultaneous determination of three common PON polymorphisms (PON1-192, PON1-55 and PON2-311) that are tightly associated with an increased risk of atherosclerosis.
A common polymorphism in the PON gene (PON1) causes an amino acid substitution of methionine (M) for leucine (L) at position 55 in the protein, which changes the activity of PON and can affect the risk of atherosclerosis.
Human serum paraoxonase (PON1) hydrolyzes oxidized lipids in low density lipoprotein (LDL) and could therefore retard the development of atherosclerosis.
The PON1 polymorphism and atherosclerosis would not appear to be associated with risk of CAA in the elderly, although further study with larger samples is necessary for confirmation.
Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established.
Our results indicate that PON1 protects against atherosclerosis in a dose-dependent manner and suggest that it may be a potential target for developing therapeutic agents for the treatment of cardiovascular disease.
Paraoxonase 1 is much the most extensively researched and strategies will hopefully emerge to increase its activity and provide a more satisfactory test of the antioxidant hypothesis of atherosclerosis than antioxidant vitamins have done.
In this investigation, we studied 120 AR patients and 90 matched controls to elucidate the association between polymorphisms in some metabolizing genes (GSTM1, GSTT1, CYP2E1, mEH, PON1, and MPO) and susceptibility to AR.