Search

Objectives Low serum PON1 activities (paraoxon, phenyl-acetate or lactone substrates) are associated with coronary heart disease (CHD). We investigated the rate of diazoxon hydrolysis by PON1 in a population with CHD. Design & methods Case- control study of 410 subjects with CHD and 274 controls. PON1 activity towards paraoxon and diazoxon, PON1 serum concentration and the PON1–55 and 192 polymorphisms were determined. Results There were no differences in the distribution of the PON1–55 or PON1–192 genotypes between the CHD and controls, however, PON1 activity towards diazoxon (DIAZ) was significantly (+160%) higher in CHD. In the control population, DIAZ was significantly different between the PON1–192 genotypes in the order QQ > QR > RR (P QR = RR. In CHD DIAZ was significantly higher in all the PON1–192 and 55 genotypes compared to controls. In both populations DIAZ was significantly different between the PON1–55 genotypes in the order LL > LM > MM (P Conclusion If this result can be replicated in other studies and/or with other PON1 substrates, there may be major diagnostic and mechanistic implications for the relationship of PON1 and CHD.

Objectives To investigate the relationships between serum paraoxonase-1 (PON1), insulin resistance, and metabolic syndrome (MetS) in childhood obesity. Design and methods We studied 110 obese children and 36 non-obese children with a similar gender and age distribution. We measured serum PON1 activity against 5-thiobutyl butyrolactone (TBBLase) and against paraoxon (paraoxonase). PON1 concentration was measured separately as were the levels of several standard metabolic variables. The homeostasis model assessment (HOMA) index was calculated as an estimate of insulin resistance. Results TBBLase was significantly decreased in obese children (P = 0.008), while paraoxonase activity and PON1 concentrations showed non-significant trends towards decrease and increase, respectively (P = 0.054 and P = 0.060). TBBLase and paraoxonase specific activities were significantly decreased (P = 0.004 and P = 0.018, respectively). TBBLase specific activity was inversely associated with BMI, percentage body fat, insulin, HOMA, triglycerides, and C-reactive protein, and directly associated with HDL-cholesterol. Paraoxonase specific activity showed similar associations with BMI, percentage fat, HDL-cholesterol, and C-reactive protein. Obese children with MetS had lower TBBLase activities than obese children without MetS (P = 0.018). Linear regression analyses showed that TBBLase was independently associated with HDL-cholesterol, BMI, percentage body fat and PON155 polymorphism, but paraoxonase activity was associated only with PON1192 polymorphism. Conclusions 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. However, being derived from statistical association study, this finding cannot be seen as showing cause–effect.

Objectives To investigate the effects of dilution on high-density lipoprotein (HDL) associated paraoxonase-1 (PON1) activity. Design and methods HDL was prepared by ultracentrifugation, diluted with TRIS buffer pH 8.2 (0–128 fold) and assayed spectrophotometrically for PON1 activity using paraoxon and phenyl acetate. Results HDL-PON1 activity increased progressively with dilution to over 200% of the undiluted activity by 128 fold dilution (P Conclusion These results indicate the urgent need to standardise conditions for measuring PON1 activity.

Objectives Research on paraoxonase-3 (PON3) has been hampered by the lack of methods for measurement. This is a pilot study aimed at exploring whether chronic liver impairment is associated with changes in serum PON3 concentrations, and to know whether this measurement may provide useful information to investigate this derangement. Design and methods We studied 110 patients with chronic liver disease (21 minimal changes, 79 chronic hepatitis, 10 cirrhosis) and 356 healthy volunteers. Serum PON3 concentration was determined by ELISA using polyclonal antibodies generated against a synthetic peptide with a sequence specific to PON3. Results Serum PON3 concentrations were increased in patients with chronic hepatitis or cirrhosis and showed significant direct correlations with the degree of periportal abnormalities including fibrosis, and with serum FAS (a marker of antiapoptosis) concentrations. Conclusion These results suggest that PON3 may play a hepatoprotective role against histological alterations and hepatic cell apoptosis leading to liver disease.

Objectives: To investigate the relationship between serum paraoxonase-1 and liver damage in chronic alcoholic patients. To assess the diagnostic accuracy of paraoxonase-1 plus standard biochemical tests in the assessment of liver damage in alcoholics. Design and methods: We studied 328 chronic alcoholics and 368 healthy individuals. Results: Paraoxonase-1 activity was decreased and the concentration was increased in alcoholics (P