Low Levels of Serum Paraoxonase Activities are Characteristic of Metabolic Syndrome and May Influence the Metabolic-Syndrome-Related Risk of Coronary Artery Disease

Abstract

Low concentrations of plasma high-density lipoprotein (HDLs) are characteristic in metabolic syndrome (MS). The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1). Different PON1 activities have been assessed in 293 subjects with (n = 88) or without MS (n = 205) and with (n = 195) or without (n = 98) angiographically proven coronary artery disease (CAD). MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC), which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44–13.10), while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47–4.46). Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD.

Paraoxonase-1 status in patients with hereditary hemochromatosis

“…For example, a cross-sectional study in more than 7,000 ostensibly-healthy volunteers showed that individuals with high serum ferritin concentrations had a higher predisposition to metabolic syndrome ( 42 ). Importantly, serum PON1 activity is decreased in metabolic syndrome ( 26,43 ), and such impairment has been reported to increase the risk of developing cardiovascular disease ( 26 ). Another fi nding of the present study is the higher frequency of patients homozygous for the R alloform of the PON1 192 polymorphism being associated with HH.…”

“…Serum PON1 TBBLase and DEPCyMCase activities were analyzed as previously reported ( 19,(24)(25)(26). Serum markers of iron metabolism, as well as other common biochemical parameters, were measured by standard methods in a RXL Dimension automated analyzer (Dade International Inc., Newark, DE).…”

Association between paraoxonase gene and stroke in the Han Chinese population

“…All three isoforms have been implicated as candidate genes for atherosclerosis and cardiovascular diseases due to their ability to attenuate lipid peroxidation, and due to their antioxidant and antiatherogenic effects [15-17]. Low levels of PON activity are thought to increase the risk of atherosclerosis [18], and thereby contribute to a predisposition towards stroke, coronary artery disease (CAD) and vascular disorders in diabetes [19-21]. Other studies have demonstrated a positive association between single nucleotide polymorphisms (SNPs) in PON genes and stroke susceptibility [22-25], although conflicting results have been seen in different ethnic groups [26-28].…”

Fenofibrate and extended-release niacin improve the endothelial protective effects of HDL in patients with metabolic syndrome

“…Other abnormalities in HDL could contribute in reducing their beneficial effects on the endothelium. Patients with metabolic syndrome have reduced paraoxonase (PON-1) levels and activity [34], an enzyme recently suggested to play a role in eNOS activation [28], and reduced HDL antioxidant capacity [35]. The present findings indicate that treatment with fenofibrate and niacin completely restores the impaired HDL-mediated endothelial protection in patients with metabolic syndrome.…”