Paraoxonase 1 Polymorphisms Research Articles

Correlation of PON1 polymorphisms with ankylosing spondylitis susceptibility: A case-control study in Chinese Han population.

Paraoxonase 1 (PON1) modulates the oxidative stress and inflammatory response, thus, it might relate to the risk of ankylosing spondylitis (AS). The aim of present study was to discover the correlation of PON1 polymorphisms (rs662 and rs854560) with PON1 activity and AS risk.Around 128 AS patients and 146 healthy controls were recruited in this case–control study. PON1 polymorphisms were genotyped by direct sequencing. Serum PON1 activity was detected and compared by nonparametric test in different genotypes of PON1 polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to present the relative risk for AS.GG genotype and G allele of rs662 polymorphism were closely correlated with enhanced AS risk (P = .034, OR = 2.318, 95%CI = 1.051–5.113; P = .032, OR = 1.485, 95%CI = 1.033–2.135). PON1 activity was obviously higher in controls than that in AS patients. Significant difference of PON1 activity has been discovered in the different rs662 genotypes (P < .01). rs662 GG genotype carriers had the lowest PON1 activity, followed by AG carriers and the AA carriers. Besides, no significant relationship existed between rs854560 genotypes and AS risk.PON1 rs662 polymorphism is significantly correlated with increased AS risk via inhibiting PON1 activity.

The genetic association between PON1 polymorphisms and osteonecrosis of femoral head: A case-control study.

The purpose of this study was to investigate the relationship between Paraoxonase-1 (PON1) gene rs662, rs854555 polymorphisms and osteonecrosis of the femoral head (ONFH) in Han population, northern China.Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of PON1 polymorphisms in 84 patients with ONFH and 96 healthy persons. χ2 test was used to compare distribution differences of genotype, allele, and haplotype between the case and control groups. The odds ratio (OR) and 95% confidence interval (CI) were calculated to reveal the effects of PON1 polymorphisms on risk of ONFH, and the results were adjusted using logistic regression analysis. The linkage disequilibrium and haplotype analysis were performed with haploview software.That people carrying AA genotype of rs662 were easier to be attacked by ONFH than GG genotype carriers (OR = 2.53, 95% CI = 1.05–6.07, P = .038). Meanwhile, the frequency of A allele in the case group was significantly higher than the controls and it was a risk factor for ONFH (OR = 1.56, 95% CI = 1.03–2.38, P = .038). The A-A haplotype frequency of rs854555-rs662 in PON1 was significantly correlated to the increased susceptibility to ONFH (OR = 2.74, 95% CI = 1.28–5.84).The rs662 polymorphism in PON1 may be associated with ONFH susceptibility, but not rs854555 in Han population, northern China. Additionally, haplotype is also a nonignorable risk factor.

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer.

We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa -high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa -low PSA and non PCa -high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa.

Association between anti-oxidant genetic risk score and metabolic syndrome in THAI subjects

Aim: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors and type 2 diabetes related to oxidative stress. Paraoxonase-1 (PON1) plays a protective role on low density lipoprotein (LDL) from oxidative damage. A PON1 polymorphism, C-108T (rs705379), has effect on PON1 expression. A mitochondrial superoxide dismutase (SOD2) catalyzes the dismutation of superoxide. Polymorphism rs4880 (C47T) in SOD2 results in Ala16Val that affects the mitochondrial targeting of SOD2 and its activity. A combination of these polymorphisms may have effect on pathophysiology leading to MetS. The aim of this study was to investigate the association of combined PON1 rs705379 and SOD2 rs4880 with the risk of MetS in Thais.

Alzheimer's Disease and Paraoxonase 1 (PON1) Gene Polymorphisms.

Background:Some studies have indicated that human paraoxonase 1 (PON1) activity shows a polymorphic distribution. The aim of this study was to determine the distribution of PON1 polymorphism in patients with Alzheimer’s disease in Gorgan and compare it with a healthy control group.Method:The study included 100 healthy individuals and 50 patients. Enzyme activity and genetic polymorphism of PON1 were determined.Result:There were significant differences in distribution of genotypes and alleles among patients and control group. The most common genotype was CT in patients and control group, while the most frequent alleles were T and C in patients and controls, respectively. There was a statistically significant variation between serum PON1 activity and –108C> T polymorphism. The highest PON1 enzyme activities in the patients and controls were found in CC, while lower enzyme activities were seen in CT and TT genotypes in both genders and age groups.Conclusion:Onset of Alzheimer’s disease may depend on different polymorphisms of the PON1 enzyme. Late or early-onset of Alzheimer’s disease may also depend on age and gender distribution, especially for arylesterase enzyme. Further studies on polymorphism of the enzyme are necessary for interpretation of possible polymorphic effects of enzyme on PON1 activity in humans.

The Q192R polymorphism of the paraoxonase-1 (PON1) gene is associated with susceptibility to gestational diabetes mellitus in the Greek population

A key factor protecting from oxidative stress in gestational diabetes mellitus (GDM) and in type 2 diabetes (T2D) is paraoxonase-1 (PON1). Inconclusive and limited data exist regarding the effect of a coding polymorphism (Q192R) of the PON1 gene in conferring susceptibility to both states. In the present study, we investigated the association between the PON1 gene and the risk for GDM in the Greek population and assessed for the first time its transcriptional efficiency. We studied 185 women with GDM and 104 non-diabetic controls for the PON1 polymorphism. For PON1 mRNA expression, peripheral leucocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the polymorphism, using real-time quantitative PCR. The RR genotype and the R allele of the PON1 Q192R polymorphism were significantly associated with an increased risk for GDM (p = 0.012 and p < 0.0001, respectively). Furthermore, there was no statistical correlation between the individual metabolic parameters tested and the three genotypes. Finally, the expression levels of PON1 mRNA in GDM patients did not exhibit any statistical difference compared with normal controls (p = 0.138). These data independently document that the Q192R polymorphism is closely associated with GDM susceptibility, while the PON1 gene expression is not impaired in GDM.

Investigation of paraoxonase 1 activity of the workers at the plant, who have long-term contact with organophosphorus compounds

Background. Liver enzyme paraoxonase 1 (PON1) plays an important role in protection the organism from toxic effects of organophosphorus compounds (OPs) via their hydrolysis whose rate and efficiency depend on PON1 serum level activity. PON1 activity is largely determined by the polymorphic variants of the PON1 gene. Effect of long-term work with exposure to the toxic OPs on the PON1 activity is almost unknown. The aim of the present work was to study the effect of long-term work with exposure to the toxic OPs on PON1 serum enzymatic activity depending on polymorphisms Q191R, L54M, C(-108)T PON1 gene. Materials and methods. PON1 serum enzymatic activity and PON1 polymorphisms were determined in men, who were categorized in 2 groups: workers of companies providing storage and disposal of the OPs (68) and control group (37). The PON1 191, PON1 55 and PON1 108 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. PON1 serum enzymatic activity was measured by a spectrophotometric method using paraoxon. Results. PON1 activity in workers with exposure to the toxic OPs relative was increased compared to the control group (p = 0,027). Differences in serum PON1 activity was shown for the carriers of certain genotypes of the PON1 gene: PON1 serum activity was higher in workers compared to controls only for LL genotype (L54M polymorphism) and C allele (C(-108)T polymorphism) carriers (p 0,001 and p = 0,002, correspondently). Conclusion. We suggest that the increase in serum PON1 activity in workers providing storage and disposal of OPs could be modulated with the polymorphic variants of the PON1 gene.

Association between paraoxonase-1 gene Q192R and L55M polymorphisms in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) in a population from Cairo of Egypt.

Paraoxonase-1 (PON1) is involved in the oxidative stress process that cause tissue damage observed in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). The aim of the present study was to investigate the association of PON1 Q192R and L55M polymorphisms with risk of SLE and associated APS among Egyptian sample. The study included 120 SLE patients (45 without APS and 75 with APS) and 120 healthy subjects. PON1 Q192R and L55M polymorphisms were genotyped by real-time PCR. No significant differences in Q192R genotypes or allele frequencies were found between patients and controls (p=0.5 and 0.1, respectively). The frequency of the 55M allele was significantly higher in SLE patients than in controls (66.6 vs. 43.3%), while the 55L allele was more frequent in controls (56.6%) than in patients (33.3%) (p=0.03). The LL genotype was more frequent in controls (21.6%) than in patients (10%) while M allele carrier genotypes (LM+MM) were more frequent among patients (90%) than controls (78.3%), p=0.04. Also, the 55M allele was more frequent in APS patients (73.3%) than in patients without APS (55.6%), p=0.004. M allele carrier genotypes (LM+MM) was significantly higher among APS patients (95.4%) than in non-APS patients (80%), p=0.008. Our results indicated that the PON1 L55M polymorphism associated with SLE and associated APS in a population from Cairo of Egypt, while the Q192R polymorphism plays no role in disease susceptibility. A large scale study to assess PON1 polymorphisms, PON1 activity, and markers of oxidative stress interaction is needed to clarify the role of PON-1 polymorphisms in the pathogenesis of SLE and associated APS.

Paraoxonase 1 (PON1) gene polymorphism and haplotype analysis in type 2 diabetes mellitus: a case–control study in the south Iranian population

Paraoxonase-1 (PON1) is involved in prevention of lipid peroxidation and has been associated with diseases characterized by high oxidative stress, such as cardiovascular disease and diabetes. It has been studied as a potential candidate gene for diabetes risk, but direct evidence from genetic association studies remains inconclusive. We performed an analysis in order to investigate the association between three PON1 polymorphisms (Q192R, L55M, and −108C>T) with type 2 diabetes mellitus (T2DM) in south Iranian population. A total of 340 individuals (171 documented T2DM patients and 169 healthy controls) were examined in this study. After DNA isolation and PCR-RFLP, the products were analyzed for L55M and Q192R polymorphisms in coding region and for −108C>T in promotor sequence of PON1. Statistical analysis showed that all genotypes of Q192R and −108C>T polymorphisms were not associated with diabetes (P > 0.05). However, in PON1 55 gene polymorphism, the allelic frequency of methionine (M) was significantly higher in T2DM patients compared to controls (37 vs. 28%, P < 0.05). In addition, a strong association was found between the LM+MM group and diabetes (P = 0.006). The results of the haplotype analysis for the combinations of the three polymorphisms in patients were shown that the haplotype L-T-R frequency was significantly lower in patients as compared to the controls with odds ratio of 0.28 (OR = 0.28, 95% CI 0.13–0.60, P = 0.0004). The most frequent haplotype in two patient and control groups was L-C-Q (31 and 30.2%, respectively). Met allele of PON1 55 gene polymorphism is an independent risk factor for T2DM and the L-T-R may represent as a protective haplotype in south Iranian population. Our results showed that the frequencies of polymorphisms of PON1 in the south Iranian population differ to some of those observed in other ethnic groups and provide useful data for epidemiological studies.

Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown.

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder. It is characterized by progressive degeneration of the motor neurons controlling voluntary movement. The underlying mechanisms remain elusive, a fact that has precluded development of effective treatments. ALS presents as a sporadic condition 90-95% of the time, i.e., without familial history or obvious genetic mutation. This suggests that ALS has a strong environmental component. Organophosphates (OPs) are prime candidate neurotoxicants in the etiology of ALS, as exposure to OPs was linked to higher ALS incidence among farmers, soccer players, and Gulf War veterans. In addition, polymorphisms in paraoxonase 1, an enzyme that detoxifies OPs, may increase individual vulnerability both to OP poisoning and to the risk of developing ALS. Furthermore, exposure to high doses of OPs can give rise to OP-induced delayed neuropathy (OPIDN), a debilitating condition akin to ALS characterized by similar motor impairment and paralysis. The question we pose in this review is: "what can we learn from acute exposure to high doses of neurotoxicants (OPIDN) that could help our understanding of chronic diseases resulting from potentially decades of silent exposure (ALS)?" The resemblances between OPIDN and ALS are striking at the clinical, etiological, neuropathological, cellular, and potentially molecular levels. Here, we critically present available evidence, discuss current limitations, and posit future research. In the search for the environmental origin of ALS, OPIDN offers an exciting trail to follow, which can hopefully lead to the development of novel strategies to prevent and cure these dreadful disorders.

Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease.

BackgroundMetabolic syndrome (MS) is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis.ObjectivesTo examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS).MethodsPatients (n = 116, 68% males) aged 56 (9) years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1), methylenotetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (ENOS), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL) were analysed by polymerase chain reaction (PCR) technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05.ResultsPolymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066), with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078).ConclusionsThe LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality that are not accounted for by traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have been shown to be involved in the pathogenesis of CV diseases. Objective: This study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D concentrations in RA patients, and to determine their association with CV risk in RA. Serum samples from 46 RA patients and 45 healthy controls were tested for PON1 R192Q genotypes and serum vitamin D concentrations. The cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease activity status were also assessed. PON1 polymorphism and low serum 25-hydroxyvitamin D were significantly associated with increased CV risk (p < 0.05). Compared to patients with either the PON1 QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased CV risk on multivariate analysis, controlling for traditional CV risk factors, C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (p < 0.05). There was a relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25-hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1 genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA patients.

The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome.

Some studies investigated the association of paraoxonase 1 (PON1) polymorphisms with polycystic ovarian syndrome (PCOS) risk. However, the result was still inconsistent. The aim of this study was to investigate whether there is an association between the PON1 polymorphisms and PCOS risk. Electronic databases, such as PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched for identification of the studies. The associations between PON1 polymorphisms and PCOS risk was quantified using ORs with 95% CIs. A total of 8 eligible studies with 2272 cases and 1811 controls were included in this meta-analysis. PON1 Leu55Met polymorphism was associated with a significantly increased risk of PCOS (OR=1.31; 95%CI, 1.10-1.55). However, no association was found in Asians and Caucasians (Table 2). We also found that PON1 Q192R polymorphism was associated with a significantly increased risk of PCOS (OR=1.81; 95%CI, 1.17-2.82). Additionally, this polymorphism increased PCOS risk in Asians (OR=1.26; 95%CI, 1.13-1.41). Furthermore, PON1 C108T polymorphism showed increased PCOS risk (OR=1.46; 95%CI, 1.08-1.97). No association between this polymorphism and PCOS risk was found in Asians and Caucasians. In conclusion, this meta-analysis suggested that PON1 polymorphisms were associated with PCOS risk.

The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome

Some studies investigated the association of paraoxonase 1 (PON1) polymorphisms with polycystic ovarian syndrome (PCOS) risk. However, the result was still inconsistent. The aim of this study was to investigate whether there is an association between the PON1 polymorphisms and PCOS risk. Electronic databases, such as PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched for identification of the studies. The associations between PON1 polymorphisms and PCOS risk was quantified using ORs with 95% CIs. A total of 8 eligible studies with 2272 cases and 1811 controls were included in this meta-analysis. PON1 Leu55Met polymorphism was associated with a significantly increased risk of PCOS (OR=1.31; 95%CI, 1.10-1.55). However, no association was found in Asians and Caucasians (Table 2). We also found that PON1 Q192R polymorphism was associated with a significantly increased risk of PCOS (OR=1.81; 95%CI, 1.17-2.82). Additionally, this polymorphism increased PCOS risk in Asians (OR=1.26; 95%CI, 1.13-1.41). Furthermore, PON1 C108T polymorphism showed increased PCOS risk (OR=1.46; 95%CI, 1.08-1.97). No association between this polymorphism and PCOS risk was found in Asians and Caucasians. In conclusion, this meta-analysis suggested that PON1 polymorphisms were associated with PCOS risk.

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.

Association between paraoxonase 1 (PON1) enzyme activity, PON1 C(−107)T polymorphism, nutritional status, and lipid profile in children

Abstract Background Paraoxonase 1 (PON1) is an enzyme that possesses anti-atherogenic and anti-inflammatory properties with serum levels determined by genetic and exogenous factors. Lower serum PON1 arylesterase activity is associated to metabolic alterations related to childhood overweight and onset and/or development of diabetes and CVD later in life. However, data on the relationship between genetic PON1 polymorphisms and nutritional status as well as lipid profile in children are limited. To investigate the distribution of the C(−107)T PON1 gene polymorphism and its relation with serum PON1 enzyme activity, nutritional status and lipid profile in children. Methods A cross-sectional study was performed including 73 children aged 5 to 7 years who attended public pediatric clinics. PON1 C(−107)T, arylesterase activity, body mass index for the age, and serum lipid profile were evaluated. Results PON1 activity was higher in overweight children compared to the normal weight ones (p = 0.02). The genotypic frequency did not differ between the two groups (p &gt; 0.05). Carriers of CC genotype had higher enzyme activity than T allele carriers, and this difference was greater among normal weight children. HDL levels were higher among normal weight children carrying CC genotype, compared to those carrying the T allele (p &lt; 0.01). Conclusion The PON1 C(−107)T polymorphism is associated with higher serum enzyme activity in children, as observed previously in adults. In addition, this polymorphism also shows association to higher high density lipoprotein (HDL) levels and serum PON1 arylesterase activity in the normal weight children studied.

The rs662 polymorphism of paraoxonase 1 affects the difference in the inhibition of butyrylcholinesterase activity by organophosphorus pesticides in human blood.

Organophosphorus pesticides (OPs) are a human health hazard. OPs inhibit acetylcholinesterase (AChE) at nerve endings and accumulate acetylcholine (ACh) at these sites. High levels of ACh and long exposure promote cholinergic crisis. The hydrolysis of OPs by serum paraoxonase 1 (PON1) plays a role in cholinergic crisis in humans. Human serum PON1 can break down organophosphate before binding to ChE. We investigated the effect of PON1 polymorphisms on AChE activity after OP treatment. 50 healthy volunteers were randomly recruited with informed consent. We investigated butyrylcholinesterase (BuChE) activity changes in plasma as a biomarker of AChE after OP treatment in human blood samples immediately following blood sampling. After the standardization of BuChE activity in human blood, we correlated changes in BuChE activity with changes in blood pH. We analyzed the PON1 polymorphisms (rs854560 and rs662) of 50 participants to retrospectively investigate the interindividual variability of changes in BuChE activity. Changes in BuChE activity are strongly correlated with pH changes after OP treatment (R2 = 0.913). We used changes in pH as a surrogate marker for BuChE inhibition after OP treatment. OP treatment significantly decreased BuChE activity by 56.4 ± 5.1% (p < 0.001). The degree of BuChE inhibition was significantly different in the PON1 rs662 genotype (56.10 ± 4.74% vs. 57.96 ± 5.67% vs. 52.34 ± 1.51%; GG vs. GA vs. AA, respectively). Changes in pH can be used as a surrogate marker for the detection of BuChE inhibition after OP exposure. The rs662 polymorphism of PON1 may explain the inter-individual variability in BuChE inhibition.

Activity and determinants of cholinesterases and paraoxonase-1 in blood of workers exposed to non-cholinesterase inhibiting pesticides

Pesticide exposure has been associated with different adverse health effects which may be modulated to some extent by paraoxonase-1 (PON1) activity and genetic polymorphisms. This study assessed seasonal variations in PON1 activity (using paraoxon –POase–, phenylacetate –AREase–, diazoxon –DZOase– and dihydrocoumarin –DHCase– as substrates), erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (using butyrylthiocholine –BuChE– and benzoylcholine –BeChE– as substrates. The study population consisted of intensive agriculture workers regularly exposed to pesticides other than organophosphates and non-exposed controls from Almería (Southeastern Spain). The effect of common genetic polymorphisms of PON1 and BCHE on paraoxonase-1 and cholinesterase activities toward different substrates was also assessed. Linear mixed models were used to compare esterase activities in agricultural workers and control subjects over the two study periods (high and low exposure to pesticides). The significant decrease in AChE and increase in BuChE and BeChE activities observed in workers with respect to control subjects was attributed to pesticide exposure. Workers also had higher levels of AREase, DZOase and, to a lesser extent, of POase, but showed decreased DHCase activity. While PON1 Q192R and PON1 -108C/T gene polymorphisms were significantly associated with all PON1 activities, PON1 L55M showed a significant association with AREase, DZOase and DHCase. BCHE-K (Karlow variant) was significantly associated with lower BeChE activity (but not with BuChE) and BCHE-A (atypical variant) showed no significant association with any cholinesterase activity. These findings suggest that increased PON1, BuChE and BeChE activities in exposed workers might result from an adaptive response against pesticide exposure to compensate for adverse effects at the biochemical level. This response appears to be modulated by PON1 and BCHE gene polymorphisms.

Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly

Background: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly.Methods: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined.Results: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 ± 63.36 U/l in the case group and 63 ± 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively).Conclusions: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.

Distribution of genetic variants of oxidative stress metabolism genes: Paraoxonase 1 (PON1) and Glutathione S-transferase (GSTM1/GSTT1) in a population from Southeastern Mexico

Background: Paraoxonase 1 (PON1) and glutathione S-transferases (GSTs) are involved in the biotransformation of xenobiotics. Variation in the enzyme concentration and activity suggests individual differences for the degree of protection against oxidative stress.Aim: This study analysed the distribution of SNPs Q192R, L55M (PON1) and variants in GSTM1 and GSTT1 genes in a population from Southeastern Mexico.Subjects and methods: One hundred and fifty-one Mexican Mestizo healthy volunteers were included. PON1 polymorphisms were determined by Taqman allele discrimination real time-PCR, whereas GSTM1 and GSTT1 genes were determined with a multiplex PCR-based method.Results: All genotypes were in Hardy-Weinberg equilibrium, except for GSTM1. The genotypic distributions of Q192R and L55M were 22% QQ, 48% QR, 30% RR, 62% LL, 34% LM and 4% MM, respectively, whereas the allele frequencies were 0.46 (Q), 0.54 (R), 0.79 (L) and 0.21 (M). The most frequent haplotype was R/L (46.7%). It was found that 31% and 9% of the individuals had the GSTM1 and GSTT1 null genotype, respectively. The frequency of the combined null genotype GSTM1*0/GSTT1*0 was 4.64%.Conclusion: The results showed that the frequencies of polymorphisms of PON1, GSTM1 and GSTT1 in the Yucatán population differ to those observed in other ethnic groups and provide useful data for epidemiological studies.