R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke.

The polymorphic gene of serum paraoxonase (PON1) and its activity involved in atherosclerosis. The purpose of the study was to analyze PON1 192 Q/R polymorphism and the enzyme activities in ischemic stroke. The polymorphism as the most common polymorphism in PON1 gene coding sequence is associated with variation in the enzyme activity and vascular disease. The study included 85 stroke patients and 71 control subjects. PON1 192 polymorphism was genotyped using PCR protocol. Paraoxonase activity (Para) and arylesterase activity (Aryl) were determined spectrophotometrically using paraoxon and phenylacetate as the substrates. The QR and RR genotypes were more frequent in stroke population compared to controls, resulting in a higher frequency of the R allele in patients (0.24 vs 0.18, OR = 1.41). Patients had significantly higher Para/Aryl ratio than that of controls (P = 0.016). In stroke patients, Para/Aryl and Para/HDL ratios increased with this order: QQ < QR < RR. Hypertension significantly increased the risk of ischemic stroke by 15-fold among R-containing people, while this was significantly increased 4-fold for QQ homozygotes. Smoking increased the risk of having ischemic stroke in both QQ homozygote and QR + RR group (OR = 2.84 and OR = 2.33, respectively). In conclusion, these data highlight the importance of PON1 192 R allele and high Para/Aryl ratio in susceptibility to ischemic stroke in the population. The presence of the 192 R allele potentiates the risk of stroke especially in hypertensive people. Decreased Aryl and increased Para/Aryl, Para/HDL and Aryl/HDL ratios may be markers indicated the increased susceptibility to ischemic stroke in the population.

Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis.

PURPOSE: Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors. METHODS: Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre-and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay. RESULTS: Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre-dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD. CONCLUSIONS: Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD.

The salt stimulation property of serum paraoxonase (PON1) could be a valuable factor in evaluating the enzyme status in ischemic stroke: the role of activity-determined PON1 192Q/R phenotypes.

Variability in the activity and function of serum paraoxonase (PON1) as an antioxidant enzyme involved in vascular disease has been observed. In this study, we investigated the enzyme activity parameters, based on the 192Q/R polymorphism, using the salt stimulation property of PON1 as an important although neglected property. In total, 172 participants, including 90 control subjects and 82 patients with ischemic stroke were enrolled. Paraoxonase activity (para), arylesterase activity (aryl) and salt-stimulated paraoxonase activity (para-Na) were measured by spectrophotometric assays. The distribution of the 192Q/R phenotypes was determined using the dual substrate method. We observed that the para-percent (percentage stimulation of paraoxonase activity by NaCl) was significantly lower in the patients than in the controls, in both the QR+RR group (p=0.01) and QQ phenotypes (p=0.001). More than the other parameters, para-percent and para-degree (para-Na-para) are affected by ischemic stroke (p<0.001). In R-containing phenotypes, significant correlations were observed between both aryl and para, with age (r=-0.364, p=0.016; and r=-0.333, p=0.029, respectively). The salt stimulation properties of PON1 activity, particularly the parameters para-percent and para-degree, could be considered more important than the prevalent activities of the enzyme, and could be better applied for the assessment of PON1 status in ischemic stroke rather than the common enzyme activities.