The PON1 Q/R polymorphism was found to have significant association with hypertension (p=0.046) and chronic constipation (p=0.028) whereas, the L/M polymorphism, with diabetes (p=0.036), arteritis (trend p=0.022) and hemorrhoids (trend p=0.027).
Our data suggest that PON1Q192R polymorphism was not independently associated with MI but further increased the risk of MI among the subjects with DM, obesity, or both, the conditions associated with high oxidative stress.
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.
Paraoxonase 1 (PON1), an arylesterase with antioxidant activity, has been shown to play an important role in preventing the development of diabetes in transgenic mice.
We showed a lower physiologically-significant lactonase PON1 activity in an Arab population, a finding consistent with the high cardiovascular and diabetes risk of Palestinians.
In recent case-control studies serum PON1 concentration and activity were also found to be decreased in coronary heart disease (CHD) independent of the PON1 polymorphism, and in diabetes serum PON1 specific activity decrease is also independent of the PON1 genetic polymorphism.
In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences.
Our results suggest that PON1 may play a role in the onset and development of metabolic alterations in childhood obesity leading to diabetes and cardiovascular disease later in life.
In the presence of metabolic syndrome and diabetes, PON1-192RR and PON2-311CC were associated with an increased risk of SCS and PON1-55MM seems to have lower risk.
In biopsy specimens, immunohistochemical analysis found increased PON1 expression on the endothelial surface of sclerotic renal arterioles and glomerular capillaries in patients with hypertension or diabetes.
Multiple linear regression analysis showed that LL genotype for PON1 (p < 0.03), high body mass index (BMI) values (p < 0.001) and low HDL-cholesterol levels (p < 0.05) are associated with high C-reactive protein levels independently from presence of stress-induced ischemia, age, sex, diabetes, hypertension, statin therapy, smoking and total cholesterol levels.
We noticed smaller PON activity decrease in our newly diagnosed diabetic subjects compared to the previous studies which investigated the alteration of enzyme activity after a longer duration of diabetes mellitus.
The serum PON1 activity was significantly decreased in the CAD group, the multiple coronary stenosis subgroup, and the diabetes mellitus subgroup compared with each control group.
Utility of sICAM-1 and PON1 as surrogate prognostic biomarkers and putative therapeutic targets in the management of diabetes and MetS is strongly suggested.
Independent associations were: 1) PON1 activity negatively with insulin resistance, triglycerides and PON1-55 genotype and positively with PON1-192 genotype; 2) PON1 concentration negatively with Caucasian ethnicity, duration of diabetes and statin use and positively with plasma creatinine and PON1-192 genotype.