L55M Polymorphisms Research Articles

Role of PON1 L55M Gene Polymorphism in Parkinson's Disease among North Indian Population.

The role of various genetic markers including alpha synuclein, Parkin, etc., is known in the pathogenesis of Parkinson's disease (PD). Novel genetic markers including paraoxonase 1 (PON1) have also been linked to PD pathogenesis in recent studies. The PON1 L55M allele carriers may have defective clearance of environmental toxins and may result in increased susceptibility to PD. Hence, we studied the role of PON1 L55M polymorphism in PD among a North Indian population. Seventy-four PD patients and 74 age- and sex-matched controls were recruited in this hospital-based case-control study. Baseline characteristics were recorded using structured questionnaire. DNA was extracted from 3-4 ml of venous blood, followed by PCR and restriction digestion. PON1 L55M genotypes were visualized as bands: LL (177 bp), LM (177, 140 bp) and MM (140,44 bp) on 3% agarose gel. Mann-Whitney U test and Chi-squared test were used for comparing two groups of skewed and categorical variables, respectively. Measures of strength of association were calculated by binary regression analysis. P value < 0.05 was considered as significant. Parkinson's disease patients had significantly higher exposure to pesticides (12.2%; P (organophosphate exposure) < 0.001) and well water drinking (28.4%; P = 0.006) compared to controls. Frequency distribution of LL, LM, MM genotypes was 67.5% (50/74), 28.4% (21/74), and 4.1% (3/74), respectively, for cases and 72.6% (54/74), 26% (19/74) and 1.4% (1/74), respectively, for controls. PON1 L55M genotype distribution between Parkinson's disease cases and controls was not significant (P = 0.53). PON1 L55M polymorphism was not associated with PD after adjusting for confounders by binary regression analysis. There was no significant association between PON1 L55M polymorphism and PD. Larger population-based studies would be required from India before drawing any definite conclusions.

Ailesel Koroner Arter Hastalığına Yatkınlıkta Güçlü Adaylar PON1, ITGB3 ve CYP3A4 Genlerinin Hastalıkla İlişkisi ve Haplotip Analizi

Objective: Genetic predisposition is very common among the patients with coronary artery disease (CAD), a complex and multifactorial disease. Our objective was to determine the possible association between the most remarkable functional variants in the paraoxonase 1(PON1), cytochrome P450 3A4 (CYP3A4), integrin subunit beta 3 (ITGB3) genes and familial CAD. Materials and Methods: We included 117 patients diagnosed with familial CAD and 99 healthy subjects with no family history of CAD. PON1 Q192R, PON1 L55M, CYP3A4*1G and ITGB3 L33P single nucleotide polymorphisms were genotyped using the Sequenom MassARRAY system. Results: Comparison of genotype and allele frequencies in inheritance models of polymorphisms between the patient and control groups did not reveal any significant findings related to CAD. Stratified analysis by gender did also not display any association both in females and males. There was no significant difference in the frequencies of the haplotypes of the PON1 Q192R and L55M polymorphisms between the groups. Conclusions: Our findings confirmed previous studies that did not consider PON1, CYP3A4 and ITGB3 genes as risk loci. The fact that our study was conducted only in patients with familial CAD shows the originality and importance of our results.

The association of paraoxonase I gene polymorphisms Q192R (rs662) and L55M (rs854560) and its activity with metabolic syndrome components in fars ethnic group.

Metabolic syndrome (MetS) may cause premature development of some diseases. PON1 genes may be involved in the pathogenesis of MetS. The aim of study was to evaluate the association between Q192R and L55M gene polymorphisms and its enzyme activity with the MetS components in subjects with and without MetS. Polymerase Chain Reaction and Restriction Fragment Length Polymorphism analysis were performed to determine polymorphisms of the paraoxonase1 gene in subjects with and without metabolic syndrome. Biochemical parameters were measured by spectrophotometer. The MM, LM, and LL genotype frequencies of the PON1 L55M polymorphism were 10.5, 43.4, and 46.1%, and 22.4, 46.6, and 31% and; the QQ, QR, and RR genotype frequencies of the PON1 Q192R polymorphism were 55.4, 38.6 and 6%; and 56.5, 34.8 and 8.7% in subjects with and without MetS, respectively. The L and M allele frequencies were 68 and 53%; and 32 and 47% for PON1 L55M in subjects with and without MetS, respectively. The Q and R allele frequencies for PON1 Q192R were 74 and 26% in both groups. There were significant differences in HDL-cholesterol level and PON1 activity in the genotypes QQ, QR, and RR of the PON1 Q192R polymorphism in subjects with MetS. The PON1 Q192R genotypes had only effected on PON1 activity and HDL-cholesterol level in subjects with MetS. Different genotypes of the PON1 Q192R seem to be important candidates to make the subjects susceptible to MetS in the Fars ethnic group.

Role of Single Nucleotide Polymorphism L55M in the Paraoxonase 1 Gene as a Risk and Prognostic Factor in Acute Coronary Syndrome.

The current work is a prospective case-control study with 77 patients with acute coronary syndrome (53 with ST-elevation myocardial infarction, STEMI, 14 with non-ST-elevation myocardial infarction, NSTEMI and 10 with unstable angina, UA) and 122 control individuals. Patients were followed-up for 9 years. The genotyping for PON1 L55M SNP was carried on by PCR-RFLP method. The results of the genotyping for PON1 L55M SNP showed a statistically significant difference (p = 0.023) between the controls and the whole group of patients with acute coronary syndrome, as the individuals with genotype with at least one variant M allele had about 2.5-fold higher risk for developing ACS than those which are homozygous of the wild-type L allele (LL genotype). In patients with variant M allele genotypes (LM + MM) which suffer from non-ST-segment elevation ACS (NSTEACS, i.e., UA or NSTEMI), the serum levels of total cholesterol (TC) and triacylglycerols (TAG) are significantly higher than in NSTEACS patients with LL genotype (p = 0.022 for TC and p = 0.015 for TAG). There was no significant difference in the survival rate at the 1st, 5th and 9th year of follow-up between ACS patients with different genotypes, although it is worth to note that in the subgroup of NSTEACS, all patients (n = 13) with variant M allele genotypes (LM + MM) were alive at the end of the first year, while 2 of the patients with LL genotype (18.2%) were dead. The results of our current study suggest that the variant M allele and the M allele genotypes (LM + MM) of the PON1 L55M polymorphism are risk factors for acute coronary syndrome, especially for patients with STEMI, but do not support the possible effect of this polymorphism on the clinical progression and outcome of the patients with ACS either in short or long follow-up periods.

Paraoxonase gene polymorphisms: Understanding the biochemical and genetic basis of coronary artery disease

ObjectivesSerum paraoxonase (PON) is a glycoprotein with antioxidant and anti-atherosclerotic activities. The Q192R and L55M gene polymorphisms of PON have been implicated as risk factors for coronary artery disease (CAD) but have not been extensively explored in South Indians. We aimed to assess the Q192R and L55M genetic polymorphisms of the PON1 gene in participants with CAD, including genotypes and allele frequencies for PON1 gene polymorphism. MethodsThis prospective case-control study involved 20 participants in each group. Patients with angiographically demonstrated CAD were included in the case group. PON1 activity was measured, and PON gene polymorphism was determined. Serum PON was quantitatively analyzed with a RayBio® Human PON1 ELISA kit. Chi square tests were used to assess the association of the genotypes with sex and any comorbidities in cases and controls. A p value ≤ 0.05 was considered significant. ResultsMutant type L55M polymorphism was observed in 50% of patients, whereas wild type Q192R polymorphism was observed in 42.5% of the participants. The mean PON values between groups did not significantly differ, whereas PON U/L was significantly (p = 0.001) lower in the case group. The L55M polymorphism did not significantly differ between the case and the control groups (p = 0.213), whereas the Q192R polymorphism was statistically significant in cases compared with controls (p ≤ 0.001) ConclusionLow plasma PON1 and HDL levels, and higher LDL, total cholesterol and triglyceride levels were observed in patients with CAD. More patients with CAD than healthy individuals had Q192R polymorphism.

Oxidative stress and PON1 (T172A/L55M) polymorphism: potential risk factors for Osteoarthritis

Objective: To investigate the role of oxidative stress in the progression of osteoarthritis with the genetic determinant of paraoxonase-1 enzyme L55M in osteoarthritis patients. Method: The case control study was carried out at the University of Karachi from April to November 2020, and comprised blood samples of female osteoarthritis patients aged &gt;50 years and healthy controls matched for age and gender. Oxidative stress was assessed by measuring lipid peroxidation product and protein carbonyl content. Activities of paraoxonase-1 paraoxonase and arylesterase were evaluated in the subjects. Protein expression of paraoxonase-1 was also analysed using western blot method. Paraoxonase-1 L55M (rs854560) polymorphism was determined using tetra-amplification-refractory mutation system polymerase chain reaction. Data was analysed using SPSS® Statistics 20.0. Results: Of the 103 subjects, 50(48.5%) were patients and 53(51.5%) were controls. The overall age range was 50-70 years. The extent of malondialdehyde (p&lt;0.001) and protein carbonyl content (p&lt;0.05) were increased significantly in the patients compared to the controls. Activity of paraoxonase and arylesterase was found decreased (p&lt;0.001) in patients compared to the controls. The prevalence of genotype MM was higher in the patients than the controls(p=0.001). L55M was more pronounced in patients suffering than the controls (p=0.01). Conclusion: The elevated levels of malondialdehyde and cabonylated protein content might be associated with osteoarthritis progression. Decreased serum paraoxonase-1 activity with L55M was the major consequence of oxidative stress in female osteoarthritis patients. Key Words: Osteoarthritis, Oxidative stress, Paraoxonase, Polymorphism.

DNA damage in a Chilean population exposed to pesticides and its association with PON1 (Q192R and L55M) susceptibility biomarker.

The active ingredients in pesticides are known to be genotoxic that can cause mutations, chromosomal aberrations, or other types of DNA damage. Early detection of genotoxicity reduces the risk of developing diseases such as cancer or suffering from reproductive disorders. In turn, the genotoxic risk depends on the intrinsic capability of the individual to metabolize and eliminate the xenobiotic from the organism. This study aimed to determine if two polymorphisms of paraoxonase-1 (PON1), which is involved in the metabolism of several organophosphate (OP) pesticides, are predictors of susceptibility to DNA damage in agricultural workers and inhabitants of rural areas chronically exposed to pesticides. A cross-sectional study was made considering three groups: agricultural workers (occupational exposure, OE, n= 85), rural inhabitants (environmental exposure, EE, n= 60), and an unexposed group conformed by people living far from agricultural areas (U, n= 33). The level of individual DNA damage was measured using the comet assay, and genotyping was done to determine the PON1 Q192R and L55M polymorphisms. Acetylcholinesterase and butyrilcholinesterase activities were also measured to determine exposure to OP. Individuals belonging to EE and OE groups displayed higher levels of DNA damage compared with U group (p< .001). OP exposure was the main predictor of genotoxicity (β=16.19; 95% CI: 1.85, 30.52), instead of PON1 polymorphisms (β=-12.20; 95% CI: -27.87, 3.48). These results confirm the genotoxic effects of pesticide exposure and suggest that the catalytic efficiency of PON1 to metabolize OP pesticides becomes negligible in individuals with a history of long-term environmental or occupational exposure to these substances.

Association Between Paraoxonase1 (Q192R and L55M) Gene Polymorphisms and Risk of Breast Cancer: A Meta-analysis of 12 Studies

Background: The paraoxonase1 gene (PON1) is part of the paraoxonase family of multifactorial antioxidants (EC 3.1.1.2). The functional single-nucleotide polymorphisms L55M and Q192R are located in the coding site of this gene. The association between these polymorphisms and breast cancer risk has been investigated, with contradictory results. Objectives: A meta-analysis was done to find the association between PON1 (L55M and Q192R) gene polymorphisms and breast cancer risk. Methods: We searched Embase, Pubmed, and Web of Science for related articles. Twelve eligible studies before December 2021 were selected. Statistical analysis was done by STATA 14.0. Result: We summarized 12 studies of L55M and Q192R polymorphisms and breast cancer risk, involving 5,769 subjects (2,519 controls and 3,250 patients). In all genetic models, PON1-L55M polymorphisms were significantly associated with breast cancer risk. Besides, PON1-Q192R polymorphisms decreased breast cancer risk. The PON1-Q192R allele reduced the cancer risk, particularly breast cancer (OR (R vs. Q): 0.7932). However, an association was found between the PON1-L55M allele and increased breast cancer risk (OR (M vs. L): 1.6041). Discussion: The results of 11 out of 12 studies were consistent with our results. In a non-conforming study, this was probably due to errors in conducting experiments. Nonetheless, well-designed studies with more samples are needed to confirm our findings at protein levels.

The effect of Paraoxonase gene polymorphisms and paraoxonase enzyme activity on Non-Hodgkin lymphoma

Non-Hodgkin Lymphoma (NHL) is a malignant lymphoproliferative disease. Antioxidant paraoxonase enzyme (PON1) has a vital role in the elimination of potential carcinogenic organophosphate molecules. The polymorphisms in the PON1 gene, especially Q192R and L55M, may affect negatively the activity and synthesis of PON1 enzyme. The aim of this study was to evaluate the effect of these polymorphisms together with PON1 enzyme activity on NHL. We surveyed these polymorphisms together with PON1 enzyme activity in 93 patients with NHL and in 93 healthy individuals by real-time polymerase chain reaction (RT-PCR) and spectrophotometer. Although carrying the M and R alleles of L55M and Q192R polymorphisms increases the risk of NHL, they were not significant. Furthermore, the NHL patients carrying 192 R allele had significantly lower enzyme activity than controls having same allele (P = 0.025). This research is the first study worldwide investigating the effect of Q192R and L55M polymorphisms on PON1 enzyme activity in NHL disease. The risk of developing NHL may be further increased in individuals with low enzyme activity having R risk allele of the Q192R polymorphism. The present study suggests that these polymorphisms in NHL disease should be analyzed together with PON1 enzyme activity in larger populations. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2022.2052315 .

Paraoxonase 1 -L55M polymorphism and coronary heart disease risk in the Chinese population: evidence from a meta-analysis

Many studies have examined the association between paraoxonase 1 (PON1) -L55M polymorphisms and risk of coronary heart disease (CHD), but the results remained inconsistent. We therefore aimed to address this association by performing an updated meta-analysis in the Chinese population. The PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure were searched up to May 2020. The strength of statistical association was assessed with odds ratio (OR) and 95% confidence interval (CI). A total of eight studies with 1826 CHD cases and 1817 controls were finally included in the analysis. In the overall and subgroup analyses by control sources and geographic areas, the results showed no significant associations with CHD among all analysis models. Furthermore, we performed the analysis by including or excluding the HWE-violating studies. The results suggested that the MM genetype were significantly associated with CHD in studies not consistent with HWE under recessive and dominant models. This meta-analysis demonstrates that the PON1 -L55M polymorphism may not be associated with CHD risk in the Chinese population. Further studies with strict selection of patients and controls in different ethnic populations will be required to clarify this finding.

Paraoxonase 1 (PON1) L55M and Q192R polymorphisms are not associated with chronic kidney disease in Thai individuals with type 2 diabetes.

Decreased paraoxonase 1 (PON1) activity and PON1 polymorphisms have been found to be associated with chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of the PON1 L55M and Q192R polymorphisms with CKD in T2DM, as well as their relationship with PON1 activity. A total of 166 T2DM patients, including 83 CKD patients and 83 non-CKD patients, were recruited. Biochemical parameters and paraoxonase (PONase) and arylesterase (AREase) activities were measured. The PON1 L55M and Q192R polymorphisms were analysed by a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data were analysed using the chi-square test, Student's t-test and logistic regression analysis. Total cholesterol, TGs, LDL-C and Cr were significantly higher in CKD patients than in non-CKD patients. In contrast, the estimated glomerular filtration rate (eGFR) and AREase activity were significantly lower in CKD patients than in non-CKD patients (P<.05). The genotype and allele frequencies of the PON1 L55M and Q192R polymorphisms were not significantly different between CKD and non-CKD patients. Multivariate logistic regression analysis showed no association between the PON1 L55M and Q192R polymorphisms and CKD in T2DM. In addition, among all patients, patients with the PON1 LM genotype had significantly lower PONase activity than those with the LL genotype (P<.05). Among all patients, CKD patients and non-CKD patients, those with the PON1 RR genotype had significantly higher PONase activity but lower AREase activity than patients with the QR and QQ genotypes (P<.05). PON1 activity was influenced by the PON1 L55M and Q192R polymorphisms. However, the PON1 L55M and Q192R polymorphisms may not be considered genetic biomarkers for CKD in T2DM.

Association of M55L and Q192R polymorphisms of paraoxonase 1 gene (PON1) with recurrent pregnancy loss risk: A case-control study.

Background Recurrent pregnancy loss (RPL) refers to the incidence of two or more abortions before the first half of pregnancy. Oxidative stress has been hypothesized to play a central role in RPL.Objective To investigate the relationship between Q192R and L55M polymorphisms of PON1 as antioxidant enzyme and the risk of RPL.Materials and MethodsIn this case–control study, 110 women with RPL (case) and 110 healthy fertile women (control) referred to the Research and Clinical Center for Infertility, Shiraz, Iran were enrolled. Genomic DNA was extracted from the peripheral blood in all participants. Polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method.ResultsStatistical analysis of Q192R polymorphism showed a significant difference for the RR genotype between the case and control group (OR = 11, CI = 1.39–86.87, p = 0.005) but none for the QR and QQ genotypes. No significant association was observed between the R and Q allelic frequency in the RPL participants compared to the control group (p = 0.53). Also, statistical analysis of the L55M polymorphism for MM genotype in the case group compared with the control group showed a significant difference (OR = 3.59, CI = 0.97–13.30, p = 0.042), but none for the LM and LL genotypes.ConclusionThe findings showed a significant correlation between the Q192R polymorphisms and the L55M PON1 enzyme and RPL in this study population.

The association between PON1 gene polymorphisms (Q192R and L55M) and nephrotic syndrome in Iraqi children

Background: The role of paraoxonase 1 enzyme (PON1) and its single nucleotide polymorphisms (SNPs) in children with nephrotic syndrome (NS) has been reported previously in different ethnic and racial groups with divergent results. The human PON1 gene contains two coding region polymorphisms leading to two different PON1 isoforms. Objectives: The aim of the present study was to find out the association between the PON1 (Q192R and L55M) polymorphisms and their relation with serum PON1 activity as well as lipid profile tests (total cholesterol, TC; triglycerides, TG; high-density lipoprotein cholesterol, HDL-c; and low-density lipoprotein cholesterol, LDL-c) in children with NS. Methods: This study included a total of 80 participants (40 with NS in the age group of 2-14 years and 40 age and sex-matched healthy controls). The PON1 enzyme activity and lipid profile tests were measured in serum samples of all included participants. The PON1 genotype was determined by PCR-restriction enzyme fragment length polymorphism (PCR-RFLP) for both PON1 alleles (192 and 55) SNPs. Results: Our findings showed that the mean levels of lipid profile tests (TC, TG, LDL-c) were significantly increased in patients when compared with healthy controls (p&lt;0.05), while the HDL-c concentration was significantly decreased in patients than that of controls. Also, the patients had significantly lower concentrations of PON1 when compared with the controls regardless of the genotype Q192R and L55M polymorphisms. Moreover, the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly frequent in patients when compared with the controls. Conclusions: Our results support that the presence of the homozygous RR genotype for PON1 SNP 192 and MM homozygous genotype for PON1 SNP 55 were significantly higher in patients compared with the controls.

Arylesterase activity of paraoxonase 1 (PON1) on HDL3 and HDL2: Relationship with Q192R, C-108T, and L55M polymorphisms

BackgroundControversy exists regarding the role of the subfractions of high-density lipoproteins (HDL2 and HDL3) in cardiovascular disease. The functionality of these particles, and their protective role, is due in part to the paraoxonase 1 (PON1) presence in them. The polymorphisms rs662 (Q192R, A/G), rs854560 (L55 M, T/A), and rs705379 (C-108T) of the PON1 gene have been related to enzyme activity and, with the anti-oxidative capacity of the HDL. The objective was to determine the arylesterase PON1 activity in HDL3 and HDL2 and its relationship with the polymorphisms mentioned, in a young population. MethodsThe polymorphisms were determined through mini-sequencing (SnaPshot). The HDL subpopulations were separated via ionic precipitation, cholesterol was measured with enzymatic methods, and PON1 activity was measured through spectrophotometry. ResultsThe results show that the PON1 polymorphisms do not influence the cholesterol in the HDL. A variation between 40.02 and 43.9 mg/dL was in all the polymorphisms without significant differences. Additionally, PON1 activity in the HDL3 subfractions was greater (62.83 ± 20 kU/L) than with HDL2 (35.8 ± 20.8 kU/L) in the whole population and in all the polymorphisms (p < 0.001), and it was independent of the polymorphism and differential arylesterase activity in the Q192R polymorphism (QQ > QR > RR). Thus, 115.90 ± 30.7, 88.78 ± 21.3, 65.29 ± 10.2, respectively, for total HDL, with identical behavior for HDL3 and HDL2. ConclusionsPON1 polymorphisms do not influence the HDL-c, and the PON activity is greater in the HDL3 than in the HDL2, independent of the polymorphism, but it is necessary to delve into the functionality of these findings in different populations.

The Role of Paraoxonase 1 (PON1) Gene Polymorphisms in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Although many studies have investigated the association of paraoxonase 1 (PON1) polymorphisms with coronary artery disease (CAD). However, the outcomes were not consistent and remain uncertain. Therefore, it is the need of the hour to analyze the available literature and evaluate the association of PON1 polymorphisms with the CAD. All the relevant studies published in the English language from January 1, 2000, up to September 20, 2020, were identified by searching through various electronic databases. The two researchers independently extracted the information. The data were analyzed by using the MetaGenyo program. The pooled odds ratio was used to find the associations between CAD and PON1 polymorphisms. In the final analysis, we include 10 studies regarding the association of PON1 polymorphisms (rs662 and rs854560) with CAD. Overall, the Q192R polymorphism increased the risk of CAD in the tested genetic models including the homozygote model: OR 1.35, CI 1.02-1.79; allelic model: OR 1.16, CI 1.00-1.33; dominant model: OR 1.25, CI 1.03-1.52. The L55M polymorphism does not significantly associated with CAD in all the tested genetic models including the homozygote model: OR 1.00 CI, 0.64-1.56; allelic model: OR 1.02, 95% CI 0.84-1.23; dominant model: OR 1.08, CI 0.89-1.31. Further analysis showed no publication bias exists in meta-analysis. Our findings suggested that rs662 in the coding region was significantly associated with the CAD however, rs854560 has no significant association with the disease. Nevertheless, in future, there is a need for more studies with a larger sample size which may provide a more definite conclusion.Study Registration: PROSPERO registration number CRD42020202278.

Organophosphate pesticide exposure, hormone levels, and interaction with PON1 polymorphisms in male adolescents

ObjectiveTo examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels. MethodsStudy subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E2], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit. ResultsMultiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E2, FSH, and AMH; detectable IMPy with increases in E2, DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers. ConclusionsIn male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype.

Associação entre os polimorfismos L55M e Q192R do gene da paraoxonase1 e a degeneração macular relacionada à idade: uma meta-análise

Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration.PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models.Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases.The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.

Relationship between PON-1 enzymatic activity and risk factors for pesticide poisoning in farmers from the Cienega, Jalisco, Mexico

Paraoxonase-1 (PON-1) is an enzyme that hydrolyzes organophosphate pesticides. The presence of polymorphisms in PON-1 (L55M and Q192R) decreases its enzyme activity and increases the risk of central nervous system (CNS) toxicity in occupationally exposed farmers, leading to chronic degenerative diseases and death. We studied 103 farmers in the region of Cienega Jalisco, Mexico, which were exposed mainly to organophosphate pesticides. We used serum and plasma samples to assay PON-1 activity and perform polymorphism analysis (L55M and Q192R) using qPCR and TaqMan probes, respectively. For both polymorphisms, there was high percentage of heterozygosity (55 LL = 0.19, LM = 0.75, MM = 0.06; 192 QQ = 0.12, QR = 0.72, RR = 0.16), while the allelic frequencies were more balanced (L = 0.56, M = 0.44; Q = 0.48, R = 0.52). There were no significant differences in enzyme activity of L55M polymorphism genotypes (LL = 179.27; LM = 192.11; MM = 122.11; QQ = 135.74; QR = 187.90; RR = 209; p > 0.05). But there was a slight decrease in enzyme activity for the Q192R polymorphism genotypes. The genotype and alcohol consumption associated with slight increases in enzyme activity. However, genotype and tobacco consumption did not have a significant effect on PON-1 activity (µU/mL) (p > 0.05). Overall, alcohol and tobacco consumption affected PON-1 enzyme activity (µU/mL) up to 21.1%. The data obtained in this study reveal that PON-1 activity is affected by genetic variants such as Q192R and alcohol consumption. This may influence the susceptibility of populations to organophosphate poisoning.

Do PON1–Q192R and PON1–L55M polymorphisms modify the effects of hypoxic training on paraoxonase and arylesterase activity?

BackgroundLow levels of antioxidant paraoxonase 1 (PON1) enzyme activity, PON1–Q192R polymorphism (a glutamine (Q) to arginine (R) substitution at position 192), PON1–L55M polymorphism (a leucine (L) to methionine (M) substitution at position 55), and oxidized low-density lipoprotein (oxLDL) are risk factors for coronary heart disease. Aerobic exercise improves PON1 activity, but the effects of hypoxic exercise are yet unclear. The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms. MethodsSerum PON1 and arylesterase activities (ARE), PON1, PON3, and oxLDL protein levels (by using the enzyme-linked immunosorbent assays) were determined in an athletic group (42 trained male underwater rugby players; age = 21.7 ± 4.2 years, mean ± SD) and a control group (43 sedentary men; age = 23.9 ± 3.2 years). The polymorphisms were determined from genomic DNA samples. ResultsPON1 activity (25.1%, p = 0.052), PON3 (p < 0.001), and oxLDL (p < 0.001) of the athletic group, including most genotype groups, were higher than those of the control group. In comparison to the controls, PON1 activity levels (p = 0.005) of the PON1–Q192R homozygote QQ genotype group and PON1 activity levels (30%, p = 0.116) of the PON1–L55M homozygote LL genotype group were higher, whereas ARE activity values of athletic R allele carrier (Rc = QR + RR) (p = 0.005) and LL group (p = 0.002) were lower than the control genotype groups related to their polymorphisms. ConclusionHypoxic training can cause (1) significant oxidative stress, including oxLDL, and an antioxidant response (increase in PON1 activity and PON3), (2) differences in the activity of PON1 and ARE, which are modified by PON1–Q192R and PON1–L55M polymorphisms, respectively, and (3) improvements in PON1 activity of QQ and LL groups. However, hypoxic training can cause a disadvantage of LL and Rc groups for ARE.

The Role of PON1 Variants in Disease Susceptibility in a Turkish Population

Paraoxonase 1 (PON1) enzyme plays a major role in antioxidant defense and protects the cells against reactive species. The most common PON1 Q192R and L55M polymorphisms are responsible for a wide variation of PON1 activity, which showed an up to 13-fold interindividual variation among the same genotype. PON1 genotypes were evaluated with the development of pancreatitis, colorectal cancer, and hypothyroidism in a hospital-based, case-control study. Individuals with rs662 G allele had a two-fold risk of developing hypothyroidism. A weak association was found between rs854560 T allele and pancreatitis. The results were preliminary. Further studies with a larger number and detailed biochemical parameters are needed.