Paraoxonase 1 Rs662 Research Articles

Association of paraoxonase-1 (Q192R) gene polymorphism with coronary artery spasm during cardiac catheterisation in Egyptians

Background Coronary artery spasm is among the etiology of myocardial infarction. Oxidative stress is involved in the pathogenesis of coronary artery spasm (CAS). Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase 1 gene might influence the pathogenesis of CAS. We aimed to investigate the association between PON1 gene polymorphism and its enzymatic activity and coronary artery spasm during cardiac catheterization. Methods and results The study population was 150 patients who underwent elective coronary angiography. Subjects were genotyped to the Q192R polymorphism (rs662) on the PON1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and PON1 activity was quantitatively analyzed by enzyme linked immunosorbent assay. Results showed that the subjects carrying the RR genotype and R allele were significantly more likely to develop coronary artery spasm (OR=4.2, 2.03, P< 0.006, P˂0.02, respectively). Moreover, serum PON1 levels were significantly decreased (P˂0.001) in the CAS group. RR genotype of PON1 Q192R polymorphism, Tc, LDLc, TG, catheter size, and paroxonase-1 serum level are independent predictors of coronary spasm. Conclusion We conclude that the PON1 (rs662) gene polymorphism is associated with CAS during cardiac catheterization in Egyptians. The PON1-192R allele and lower serum enzyme concentration may play an important role in coronary spasm.

Phospholipid metabolism-related genotypes of PLA2R1 and CERS4 contribute to nonobese MASLD.

Abnormal phospholipid metabolism is linked to metabolic dysfunction-associated steatotic liver disease (MASLD) development and progression. We aimed to clarify whether genetic variants of phospholipid metabolism modify these relationships. This case-control study consecutively recruited 600 patients who underwent MRI-based proton density fat fraction examination (240 participants with serum metabonomics analysis, 128 biopsy-proven cases) as 3 groups: healthy control, nonobese MASLD, and obese MASLD, (n = 200 cases each). Ten variants of phospholipid metabolism-related genes [phospholipase A2 Group VII rs1805018, rs76863441, rs1421378, and rs1051931; phospholipase A2 receptor 1 (PLA2R1) rs35771982, rs3828323, and rs3749117; paraoxonase-1 rs662 and rs854560; and ceramide synthase 4 (CERS4) rs17160348)] were genotyped using SNaPshot. The T-allele of CERS4 rs17160348 was associated with a higher risk of both obese and nonobese MASLD (OR: 1.95, 95% CI: 1.20-3.15; OR: 1.76, 95% CI: 1.08-2.86, respectively). PLA2R1 rs35771982-allele is a risk factor for nonobese MASLD (OR: 1.66, 95% CI: 1.11-1.24), moderate-to-severe steatosis (OR: 3.24, 95% CI: 1.96-6.22), and steatohepatitis (OR: 2.61, 95% CI: 1.15-3.87), while the paraoxonase-1 rs854560 T-allele (OR: 0.50, 95% CI: 0.26-0.97) and PLA2R1 rs3749117 C-allele (OR: 1.70, 95% CI: 1.14-2.52) are closely related to obese MASLD. After adjusting for sphingomyelin level, the effect of the PLA2R1 rs35771982CC allele on MASLD was attenuated. Furthermore, similar effects on the association between the CERS4 rs17160348 C allele and MASLD were observed for phosphatidylcholine, phosphatidic acid, sphingomyelin, and phosphatidylinositol. The mutations in PLA2R1 rs35771982 and CERS4 rs17160348 presented detrimental impact on the risk of occurrence and disease severity in nonobese MASLD through altered phospholipid metabolism.

Joint Effects of Dietary Patterns and Paraoxonase1 rs662 Polymorphism on Coronary Artery Disease Severity (Gensini and SYNTAX Scores) and Its Risk Factors in adults Undergoing Angiography.

The present study aims to assess the interaction of dietary patterns (DPs) and paraoxonase1 (PON1) rs662 polymorphism on coronary artery disease (CAD) severity and its risk factors. This cross-sectional study is conducted on 425 patients undergoing angiography. The PON1 genotypes are detected by the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique. DPs are extracted by exploratory factor analysis. Two dietary patterns Western (WDP) and Traditional (TDP) are extracted. A gene-diet interaction concerning a high Gensini score is observed. Accordingly, high adherence to the WDP increases the odds of a high Gensini score in R allele carriers compared to QQ genotype carriers by 2.48 times (odds ratio [OR]: 2.48, 95% confidence interval [CI] 0.98-6.26, p = 0.05). Also, the risk of high systolic blood pressure (SBP) is higher in R allele carriers with high adherence to the WDP compared to QQ genotype carriers(OR: 3.49, 95% CI 1.38-8.82, p<0.001. No significant interaction is observed between TDP and PON1 rs662 on any cardiometabolic risk factors (p-value>0.05). The results remain significant after adjusting for confounders. The present study's findings indicate the existence of an interaction between the PON1 rs662 polymorphism and the WDP on the risk of stenosis severity and high SBP.

Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.

CDKN2B-AS (rs2891168), SOD2 (rs4880), and PON1 (rs662) polymorphisms and susceptibility to coronary artery disease and type 2 diabetes mellitus in Iranian patients: A case-control study.

Coronary artery disease (CAD) is a devastating illness and primary cause of death worldwide that arises from a combination of genetic and environmental factors. Several large-scale studies found that 9p21.3, superoxide dismutase 2 (SOD2), and paraoxonase 1 (PON1) polymorphisms increase type 2 diabetes mellitus (T2DM) and/or coronary artery disease (CAD) risk. Our research aimed to investigate whether the SNPs of the 9p21.3 locus (rs28911698), SOD2 (rs4880), and PON1 (rs662) genes were associated with the risk of T2DM and/or CAD in the Iranian population. In this case-control study four group subjects including patients with CAD non-T2DM, with CAD and T2DM, non-CAD with T2DM, and non-CAD non-T2DM were recruited to the study from 2019 to 2020. Molecular analysis was carried out by allele specific-polymerase chain reaction (AS-PCR) technique for rs4880, Taqman genotyping assay for rs2891168, and PCR followed by restriction fragment length polymorphism (PCR-RFLP) technique for rs662. The rs2891168 polymorphism presented an elevated risk of CAD in non-T2DM with CAD and with T2DM CAD groups compared to the non-T2DM non-CAD group with GG genotype and dominant model after adjustment (p < 0.05). G-allele in PON1 rs662 polymorphism associated with increased risk of T2DM in T2DM non-CAD, and T2DM CAD groups compared to non-T2DM non-CAD group with dominant model, GG and AG genotypes (p < 0.05). However, SOD2 rs4880 polymorphism presented no significant association with the development of diabetes or CAD. These results provide a prime witness that rs2891168 and rs662 gene variants might have a possible increased risk of CAD and T2DM occurrence, respectively. To obtain more definitive and accurate results in this area, further research is required.

The association of PON1 and NOS3 genetic variants with the severity of COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) is a global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) of paraoxonase 1(PON1) and nitric oxide synthase 3 (NOS3) genes with the severity of COVID-19. Study subjects were divided into mild and severe groups. Genotyping was conducted by allele specific real-time polymerase chain reaction (RT-PCR). Gene-gene interaction was assessed by multifactor dimensionality reduction (MDR) analysis. The results showed a significant association of both PON1 rs662 (A575G), and NOS3 rs2070744 (T786C) with the severity of COVID-19 (p = 0.0026, and p = 0.033, respectively). PON1 575AG (OR = 0.30, 95 % CI [0.13–0.68]) and NOS3 786TC (OR = 0.35, 95 % CI [0.15–0.78]) were associated with mild COVID-19 symptoms. The resulted SNP-SNP interaction model by MDR analysis was statistically significant (p = 0.0003). NOS3 786C * PON1 575G haplotype was significantly associated with mild cases of COVID-19 (p = 0.045).

Vitamin E intake and paraoxonase 1 (PON1) rs662 genetic polymorphism are associated with colorectal cancer risk in a Korean population

Vitamin E and paraoxonase 1 (PON1) are associated with cancer development. However, their interactive effect on colorectal cancer (CRC) risk is inconclusive. We conducted a case–control study including 1,351 CRC patients and 2,670 controls at the Korean National Cancer Centre (KNCC). There was an inverse association between vitamin E intake and CRC risk (odds ratio (OR) = 0.31; 95% confidence interval (CI) = 0.22–0.42). We identified a reduced CRC risk among individuals with CC genotype of PON1 rs662 polymorphism compared with subjects carrying the T allele (OR = 0.74; 95% CI = 0.61–0.90). The highest interaction between vitamin E intake and PON1 rs662 variants was significant for the subjects carrying the CC genotype (p-interaction = 0.014). This study provided further supporting evidence that vitamin E intake is associated with lower odds of CRC. Furthermore, the activity of vitamin E is strengthened among individuals carrying C allele of the PON1 rs662 polymorphism.

Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson's Disease.

Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD), which often progresses to PD dementia. PD patients with and without dementia may differ in certain biochemical parameters, which could thus be used as biomarkers for PD dementia. The enzyme paraoxonase 1 (PON1) has previously been investigated as a potential biomarker in the context of other types of dementia. In a cohort of PD patients, we compared a group of 89 patients with cognitive impairment with a group of 118 patients with normal cognition. We determined the kinetic parameters Km and Vmax for PON1 for the reaction with dihydrocoumarin and the genotype of four single nucleotide polymorphisms in PON1. We found that no genotype or kinetic parameter correlated significantly with cognitive impairment in PD patients. However, we observed associations between PON1 rs662 and PON1 Km (p < 10-10), between PON1 rs662 and PON1 Vmax (p = 9.33 × 10-7), and between PON1 rs705379 and PON1 Vmax (p = 2.21 × 10-10). The present study is novel in three main aspects. (1) It is the first study to investigate associations between the PON1 genotype and enzyme kinetics in a large number of subjects. (2) It is the first study to report kinetic parameters of PON1 in a large number of subjects and to use time-concentration progress curves instead of initial velocities to determine Km and Vmax in a clinical context. (3) It is also the first study to calculate enzyme-kinetic parameters in a clinical context with a new algorithm for data point removal from progress curves, dubbed iFIT. Although our results suggest that in the context of PD, there is no clinically useful correlation between cognitive status on the one hand and PON1 genetic and enzyme-kinetic parameters on the other hand, this should not discourage future investigation into PON1's potential associations with other types of dementia.

Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications.

In this study, we aimed to investigate the effect of paraoxonase 1 (PON1) rs662 polymorphism, arylesterase (ARE) activity, and the serum lipid profile in patients with coronavirus disease 2019 (COVID-19) in different stages of the disease considering post-COVID outcomes. A total of 470 COVID-19 patients (235 female and 235 male patients) were recruited into the study, and based on the World Health Organization (WHO) criteria, the patients were divided into three groups: moderate, severe, and critical. PON1 rs662 polymorphism was determined by the Alw 1 enzyme followed by agarose gel electrophoresis. Moreover, serum levels of triglycerides (TG), cholesterol (Chol), high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c), as well as the level of the ARE activity of PON1 in the sera of patients were measured at the time of infection and one and three months after hospitalization. There was a significant relationship between the G allele and the severity of the disease. In addition, the probability of death in homozygous individuals (GG) was higher than in heterozygous patients (GA), and it was higher in heterozygous patients than in wild-type individuals (AA). There was also a significant relationship between the decrease in serum lipids and the intensity of COVID-19. On the contrary, at the onset of the disease, the HDL-c level and serum ARE activity were reduced compared to one and three months after COVID-19 infection. The findings of this study indicated the significant impact of PON1 rs662 polymorphism on ARE activity, lipid profiles, disease severity, and mortality in COVID-19 patients.

Association between PON1 rs662 gene polymorphism and serum paraoxonase1 level in coronary artery disease patients in Northern India

BackgroundCoronary artery disease (CAD) is a leading cause of morbidity and mortality, with a shifting trend towards the younger population. Paraoxonase1 (PON1) is a glycoprotein enzyme associated with high-density lipoprotein (HDL) particles in the blood. It has the ability to protect against lipid oxidation, thereby reducing the risk of atherogenesis. PON1 rs662 gene polymorphism may affect serum PON1 levels as well as its activity and may have a significant role in the pathogenesis of CAD. The present study was conducted to identify the association of PON1 rs662 gene polymorphism with serum PON1 levels in CAD patients in the North Indian population. This case–control study included 71 angiography-proven CAD patients (with > 50% luminal stenosis in one or more coronary arteries) and 71 controls (with < 50% luminal obstruction in angiography). PON1 rs662 gene polymorphism was studied using PCR and RFLP under the standardized protocol. Serum PON1 levels were estimated by ELISA.ResultsThe serum PON1 level was significantly lower in the CAD group than in the controls (7.79 ± 3.16 vs. 10.79 ± 3.19 ng/mL; p < 0.0001). Logistic regression analysis showed that homozygous GG genotype of PON1 rs662 SNP has ninefold increased risk of developing CAD in an Indian population (OR = 9.0, 95%CI 2.79–29.06, p = 0.0002). A significantly higher frequency of G allele was also observed in CAD patients than in controls (OR 2.64, 95%CI 1.61–4.33, p = 0.001).ConclusionsThe reduced serum PON1 level is associated with CAD. PON1 rs662 gene polymorphism is significantly associated with CAD susceptibility in the North Indian population.

Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis.

Objective:Breast cancer is the most common cancer in American women, except for skin cancers. In this meta-analysis, the associations of polymorphisms within paraoxonase 1 (PON1), leptin (LEP) and leptin receptor (LEPR) genes with susceptibility to breast cancer were comprehensively evaluated. Methods:A universal search in PubMed, Scopus, CNKI, SID, Web of Knowledge and Google Scholar was performed to identify relevant studies up to 01 May, 2021. The strength of the associations was estimated by Odds ratios (ORs) with 95% confidence intervals (95% CIs). Results:A total of 39 case-control studies including 7 studies with 2005 cases and 2748 controls were on PON1 rs662, 6 studies with 2,031 cases and 1,973 controls on PON1 rs854560, 12 studies with 3,444 cases and 3,583 controls on LEP rs7799039, and 14 studies with 5,330 cases and 6,188 controls on LEPR rs1137101 were selected. Pooled data showed that PON1 rs662 and rs854560 polymorphisms were associated with risk of breast cancer in overall population, but not LEP rs7799039 and LEPR rs1137101. Conclusions:Our pooled data revealed that the PON1 rs662 and rs854560 polymorphisms were significantly associated with an increased risk of breast cancer in the overall population. However, LEP rs7799039 and LEPR rs1137101 polymorphisms were not associated.

Association of SRB1 and PON1 gene polymorphisms with type 2 diabetes mellitus: a case control study

Single-nucleotide polymorphism (SNP) in Paraoxonase 1 (PON1) and scavenger receptor class b member 1 (SRB1) gene has been associated with impairing high-density lipoprotein (HDL) functionality as an antioxidant and shown to diminish ability of PON1 in cholesterol homeostasis. Several studies found that SRB1 and PON1 polymorphism increases T2DM risk. Our study aimed to investigate the association and susceptibility of polymorphic variants in SRB1 rs9919713 and PON1 rs662 with type 2 diabetes mellitus. In the present case-control study, 250 type 2 diabetes mellitus patients (T2DM) and 250 healthy volunteer were recruited. The genotypes of PON1 and SRB1 were determined by using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique, and biochemical analysis was done using standard protocol. C and R alleles showed significant association with T2DM susceptibility with an odds ratio of 1.42 (p < 0.005) and 1.40 (p < 0.007), respectively. The frequency of CC and RR genotype was significantly higher in T2DM patients compared with healthy controls. Furthermore, CC and RR genotypes were significantly associated with higher LDL and low HDL levels. Additionally, no other significant association was observed. We conclude that the PON1 and SRB1 gene polymorphisms may probably surrogate biomarkers for T2DM susceptibility.

A meta-analysis of the relationship between paraoxonase 1 polymorphisms and cancer

Some previous studies already explored associations between paraoxonase 1 (PON1) polymorphisms and cancer, with conflicting findings. Here, we aimed to better analyse the relationship between PON1 polymorphisms and cancer in a larger combined population by performing a meta-analysis. We searched PubMed, Embase, and Web of Science for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between PON1 polymorphisms and cancer. Forty studies were included for this meta-analysis. The PON1 rs854560 polymorphism (L55M) was found to be significantly associated with cancer in general population (dominant comparison: p = .04, OR = 0.85, 95%CI 0.73–0.99; recessive comparison: p = .007, OR = 1.27, 95%CI 1.07–1.51; allele comparison: p = 0.02, OR = 0.85, 95%CI 0.75–0.97). Subgroup analyses indicated that the significant findings were mainly driven by the haematological tumours and breast cancer subgroups. We did not observe any positive findings for PON1 rs662 polymorphism (Q192R) in combined analyses. In summary, this meta-analysis proved that PON1 rs854560 polymorphism could be used to identify individual with elevated susceptibility to cancer, especially for haematological tumours and breast cancer.

A meta-analysis on relationship between paraoxonase 1 polymorphisms and atherosclerotic cardiovascular diseases

BackgroundSome previous studies already explored associations between paraoxonase 1 (PON1) polymorphisms and atherosclerotic cardiovascular diseases (ASCVD), with conflicting findings. Here, we aimed to better analyze the relationship between PON1 polymorphisms and ASCVD in a larger combined population by performing a meta-analysis. MethodsWe searched Pubmed, Embase and Web of Science for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between PON1 polymorphisms and ASCVD. ResultsOne hundred and nine studies were included for this meta-analysis. The PON1 rs854560 (17,220 cases and 18,570 controls, recessive comparison: OR = 0.83, 95%CI 0.72–0.96) and rs662 (30,717 cases and 54,894 controls, dominant comparison: OR = 0.82, 95% CI 0.77–0.89; recessive comparison: OR = 1.17, 95% CI 1.07–1.28; allele comparison: OR = 0.85, 95% CI 0.81–0.90) polymorphisms were both found to be significantly associated with susceptibility to ASCVD in general population. Subgroup analyses by ethnicity revealed similar significant findings for rs854560 polymorphism only in East Asians, while similar positive findings for rs662 polymorphism were observed in Caucasians, East Asians and South Asians. Subgroup analyses by type of disease indicated that the significant findings for rs854560 polymorphism were mainly driven by the ischemic stroke (IS) subgroup, whereas the positive results for rs662 polymorphism were mainly driven by the coronary artery disease (CAD) subgroup. ConclusionsIn summary, this meta-analysis proved that PON1 rs854560 polymorphism could be used to identify individual with elevated susceptibility to IS, whereas rs662 polymorphism could be used to identify individual with elevated susceptibility to CAD.

Significant association between paraoxonase 1 rs662 polymorphism and coronary heart disease : A meta-analysis in the Chinese population.

Agrowing number of studies have suggested that the single nucleotide polymorphism (SNP) rs662 (G>A) in paraoxonase1 (PON1) is significantly associated with susceptibility to coronary heart disease (CHD) in the Chinese population. To further evaluate the effects of the PON1 RS662 (G>A) polymorphism on the risk of CHD, we performed ameta-analysis in aChinese population. PubMed, Embase, Wanfang Data, Chinese National Knowledge Infrastructure (CNKI) were searched to identify eligible studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations between RS662 (G>A) and CHD. In the meta-analysis, we identified 14articles, including atotal of 4835CHD patients and 5111controls in the Chinese population. Our result showed that overall rs662 (G>A) was significantly associated with susceptibility to CHD in the Chinese population when compared with healthy controls. Furthermore, aGallele suggested an elevated risk of CHD. In the subgroup analyses stratified by ethnicity and geographic areas, significant associations were found in Chinese Han and South China, but not in North China. The present meta-analysis suggests that rs662 (G>A) SNP in PON1 is associated with CHD risk; the Gallele might be the risk allele for CHD susceptibility in the Chinese population. However, more research is required to make adefinite conclusion.

Association between Paraoxonase 1 polymorphisms and risk of esophagogastric junction adenocarcinoma: a case-control study involving 2,740 subjects.

Esophagogastric junction adenocarcinoma (EGJA) is a serious public health problem with high mortality in China. In this study, we assessed the association between Paraoxonase 1 (PON-1) rs662 C>T, rs854560 A>T polymorphisms and EGJA risk. This case-control study enrolled 2,740 participants of Asians origin from the Eastern Chinese Han populations. SNPscanTM genotyping assay was harnessed to determine the genotyping of PON1 polymorphisms. The PON-1 rs854560 A>T and rs662 C>T genotypes distribution accorded with Hardy–Weinberg equilibrium. We found that there was no difference in the frequency of PON-1 rs662 C>T, rs854560 A>T genotypes between the overall EGJA cases and controls. In the subgroup analyses, the results indicated that PON-1 rs662 C>T polymorphism might be associated with a significantly decreased risk of EGJA in ever smoking group (TT vs. CC/CT: adjusted OR = 0.58, 95% CI 0.35–0.95, P = 0.029). In conclusion, our study highlights PON-1 rs662 C>T polymorphism may decrease the risk of EGJA, which interacts with the tobacco using. In the future, a fine-mapping case-control study with detailed gene-environmental data is needed to further assess these potential relationship.

GENOTYPES AND SERUM LEVELS OF APOLIPOPROTEIN E AND PARAOXONASE 1 IN CALCIFIC AORTIC VALVE STENOSIS

Aim. Apolipoprotein E (apoE) and paraoxonase 1 (PON1) participate in regulation of blood lipoprotein levels, as well as in their hydrolysis and oxidation. We assumed that individual alleles of the apoE and PON1 genes, along with the changes in concentrations of these substances, contribute to the development of calcific aortic valve stenosis (CAVS). Material and methods. The study group included 108 patients with CAVS and 46 patients without any signs of the aortic valve lesions were determined. The serum apoE and PON1 levels were measured by ELISA, the Leu28Pro mutation in the apoE (rs429358) gene and the Gln192Arg mutation in the PON1 (rs662) gene were detected using PCR SNP-EXPRESS electrophoresis detection scheme. Results. Increased serum levels of apoE (0,05 vs 0,03 µg/l, p&lt;0,001) and PON1 (4,8 vs 3,4 µg/ml, p&lt;0,05) were detected in CAVS patients. The frequencies of allelic polymorphisms of the apoE and PON1 genes were similar in the two groups. 28Pro allele of the apoE gene was associated with increased level of low density lipoproteins in CAVS (3,9±1,05 vs 3,13±1,08 mmol/l, p&lt;0,02) and total cholesterol in the controls (6,2; 6,5 vs 5,11±0,89 mmol/l, p&lt;0,05). The PON1 genotype had no effect on lipid metabolism in CAVS patients. Controls with 192Gln allele demonstrated decreased blood levels of apoE (0,02 vs 0,05 µg/l, р&lt;0,01) and increased PON1 serum concentration (4,1 vs 3,3 µg/ml, р&lt;0,01). Conclusions. CAVS patients have increased serum levels of apoE and PON1; the apoE level is an independent predictor of aortic calcification. Polymorphic markers Gln192Arg of the PON1 gene and Leu28Pro of the apoE gene are not associated with CAVS.

Serum Levels of Anti-PON1 and Anti-HDL Antibodies as Potential Biomarkers of Premature Atherosclerosis in Systemic Lupus Erythematosus.

The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quantified in serum samples from 198 SLE patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in a subgroup of patients and controls. Subclinical CVD were determined by Doppler ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media thickness (IMT) and blood flow parameters in internal carotid, middle cerebral and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were increased in SLE patients compared with HC (p < 0.001); however, only anti-PON1 antibodies, in addition to disease activity, were significant predictors of the impaired PON1 function in SLE (β = -0.143, p = 0.045). Conversely, anti-HDL antibodies were associated with higher risk of CVD (odds ratio: 3.69; p = 0.012) and lower HDL levels at disease onset (ρ = -0.324, p = 0.044). Finally, anti-PON1 antibodies were associated with carotid IMT in SLE (β = 0.201, p = 0.008) and inversely related to cranial arteries blood flow velocities in patients with clinical and subclinical CVD (all p < 0.001). In sum, these findings allowed us to propose serum levels of anti-PON1 and anti-HDL antibodies as potential early biomarkers of endothelial damage and premature atherosclerosis in SLE, thus constituting useful therapeutic targets for the prevention of future CVD in these patients.

Paraoxonase-1 (PON1) rs662 Polymorphism and Its Association with Serum Lipid Levels and Longevity in the Bama Zhuang Population.

BackgroundThe present study was performed to identify the association of PON1 rs662 polymorphism with serum lipid levels and human longevity in the Bama Zhuang population.Material/MethodsPON1 genotypes were determined by Taqman SNP Genotyping Assays in 110 long-lived inhabitants (longevity group, aged 90–110 years), 110 healthy inhabitants in Bama County (control 1 group, aged 43–82 years) and 110 healthy inhabitants in Nandan County (control 2 group, aged 28–82 years) without family history of longevity.ResultsBMI (body mass index) and TG (serum total triglyceride) level were lower in the longevity group than in the two control groups, while the contents of serum LDL-c (low-density lipoprotein cholesterol) and HDL-c (high-density lipoprotein cholesterol) and the levels of SBP (systolic blood pressure) and DBP (diastolic blood pressure) in the longevity group were higher than in the two control groups (p<0.01). Significant differences in the frequencies of three genotypes (GG, AG, and AA) were observed between the longevity group and control 2 group (χ2=15.190, p=0.001). The minor allele frequency (MAF) of rs662 was significantly higher in the longevity group than in the two control groups. The levels of HDL-c in the longevity group were different among the three genotypes (p<0.05). The levels of TG for GG and GG+AG genotypes were significantly different, while the levels of TC (total cholesterol) and HDL-c for AG and GG+AG genotypes were significantly different among the three groups (p<0.05). Serum lipid parameters were correlated with several environmental factors, including age, gender, DBP, SBP, and BMI. The association of PON1 rs662 polymorphism and serum lipid levels was different among the three groups.ConclusionsPON1 polymorphism might be one of the genetic factors of longevity in the Bama Zhuang population. The PON1 rs662 SNP (single nucleotide polymorphism) was associated with serum HDL-c levels in the longevity group.

Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis.

Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of high-density lipoprotein (HDL) has been observed. Although the actual players are unknown, anti-HDLs were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA. Therefore, we aimed to evaluate whether the presence of antibodies against PON1 may be involved in this scenario. IgG anti-PON1 antibodies were quantified by ELISA in serum samples from 212 RA patients, 175 healthy controls (HC) and 54 subjects with traditional CV risk factors (CVR). A subgroup of 13 RA patients was prospectively followed upon tumour necrosis factor-α (TNFα) blockade. Serum PON1 activity, nitric oxide (NO) and total antioxidant capacity (TAC) were measured. Interferon-γ (IFNγ), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule (sICAM) and TNFα serum levels were assessed by immunoassays. PON1 rs662 (Q > R) status was studied by reverse transcription (RT)-PCR. IgG anti-PON1 antibodies are increased in RA patients compared with HC (P<0.0001) and CVR subjects (P<0.001), even after correcting for total IgG levels. Although no associations with lipid profile were found, a positive correlation with Health Assessment Questionnaire (HAQ) was observed (r=0.215, P=0.004). Anti-PON1 antibodies were associated with PON1 activity, NO and TAC, a rs662-mediated gene-dosage effect being found. Similarly, anti-PON1 antibodies were associated with sICAM serum levels in univariate and multivariate models. Finally, these antibodies were not affected by TNFα blockade. Anti-PON1 antibodies can be responsible for PON1 impairment in RA patients, with a potential impact on biomarkers of oxidative status and endothelial activation. A gene-environment interaction of rs662 variants is supported.