Paraoxonase 1 Q192R Polymorphism Research Articles

The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.

Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity. The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity. The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity. The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.

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.

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 the paraoxonase 1 Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD.

The present study aimed to investigate the association of the paraoxonase 1 (PON1) Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD. This cross-sectional study was conducted on 428 patients undergoing angiography. The data related to demographic information and physical activity were collected by valid and reliable questionnaires. The PON-1 genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique. The Gensini and SYNTAX score, anthropometric measurements, and biochemical and clinical parameters were measured by standard protocols. Findings indicated that the odds of obesity was significantly higher in people with the RR genotype compared to the QQ genotype carriers (OR: 2.95 CI: 1.25-6.93, P = 0.014) and also odds of low high-density lipoprotein cholesterol (HDL-C) was marginally higher (OR: 2.31 CI: 0.97-5.49, P = 0.056). There was no significant association between other CAD risk factors with PON1 Q192R polymorphism (P > 0.05). Further analysis showed a significant interaction between sex and 192QR (P = 0.019) and 192 RR (P = 0.007) genotypes on body mass index (BMI). More specifically, the risk of obesity in men carrying the RR genotype was 3.38 times (OR: 3.38 CI: 1.08-10.58, P = 0.036). Also, a significant joint effect of the RR genotype and sex on HDL-C was seen (P = 0.003). The stratification based on sex showed that the risk of low HDL-C is significantly higher in women carrying the RR genotype (OR: 6.18 CI: 1.21-31.46, P = 0.028). A marginal sex-genotype interaction was also found in the risk of elevated alanine aminotransferase (ALT) (P = 0.057). In summary, the findings showed that the risk of obesity and low HDL-C was higher in people carrying the RR genotype. On the other hand, a Q192R polymorphism-sex interaction was observed on the risk of obesity, elevated ALT, and low HDL-C.

Suppressed paraoxonase-1 activity associates with elevated oxylipins and the presence of small airways disease in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA)-associated lung disease (LD) associates with significantly increased morbidity and mortality. Although oxidative stress plays an important role in the inflammatory responses in other forms of lung disease, minimal work has evaluated its role in RA-LD. The current work examines the relationship between the anti-oxidant HDL-associated enzyme paraoxonase-1 (PON1), the PON1 Q192R polymorphism, and a targeted oxylipin panel with RA-LD.MethodsThis study was conducted as a retrospective chart review of a longitudinal single-center cohort of 250 RA patients. CT scans of the chest were reviewed by the interpreting radiologist and classified as small airways disease (SAD), interstitial lung disease (ILD), and bronchiectasis. PON1 activity was measured by its lactonase, arylesterase, and paraoxonase functions. The PON1 Q192R polymorphism and a targeted lipidomics panel were performed as previously reported.Results43.2% of the 250 RA patient cohort (n = 108) had available CT scans, including 48 patients (44.4%) with SAD, 27 patients (25.0%) with bronchiectasis, and 16 patients (14.8%) with ILD. Patients with SAD had significantly lower baseline PON1 activity by its arylesterase, and lactonase functions, as well as higher 15-HETE, LTB4, and PGE2 levels compared to those without SAD. These predictors of SAD remained significant after multivariate analysis including known risk factors for RA-LD. Suppressed PON1 activity also correlated with higher levels of 15-HETE and 12-HETE.ConclusionIn a single-center RA cohort, suppressed baseline PON1 activity and elevation in the oxylipins 15-HETE, LTB4, and PGE2 predicted the presence of RA-SAD in longitudinal follow-up.Key Points• Small airways disease (SAD) was present in 44.4% of this rheumatoid arthritis (RA) cohort.• Patients with SAD had significantly lower baseline PON1 activity, as well as higher levels of the oxylipins 15-HETE, LTB4, and PGE2 levels compared to those without SAD.• Further work is warranted to confirm these findings and further define the role of PON1 and lipid oxidation in RA lung disease.

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.

Paraoxonase-1 Q192R Polymorphism and Lipid Peroxidation and Antioxidant Defense State in Russian Healthy Teenagers

Paraoxonase-1 Q192R Polymorphism and Lipid Peroxidation and Antioxidant Defense State in Russian Healthy Teenagers

Paraoxonase 1: Could it be important for asthma in children?

Objective: The paraoxonase 1 (PON-1) enzyme is an important antioxidant. The balance between oxidative stress and antioxidant defense mechanisms is disturbed during asthma attacks. The activity of the PON-1 enzyme is related to PON-1 gene polymorphism. This study aimed to evaluate the activity of PON-1 enzyme and Q192R polymorphism in asthmatic children. Material and methods: During the 2013-2014 period, we performed a prospective study with 34 asthmatic (study group) and 34 healthy (control group) children. Serum PON-1 activity was evaluated in the study group at the onset of an asthma attack and at the end, and also in the control group. Q192R gene polymorphism of asthmatic children, which is known to affect the PON-1 enzyme activity was also investigated. Results: There was no significant difference in terms of serum PON-1 enzyme activity and PON-1 gene polymorphism between the asthmatic children and healthy controls. However, a significant increase was observed at the PON-1 enzyme activity of asthmatic children at the end of the asthma attack compared to its onset. Conclusion: The PON-1 enzyme activity and Q192R genetic polymorphism in asthmatic children are not different from those of healthy children, but PON-1 enzyme activity is higher at the end of an asthma attack compared to the onset. PON-1 enzyme, as a member of the antioxidant mechanism, may be important both in understanding the pathophysiology of asthma and in the development of new medications for asthma.

Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies.

Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients. A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes. The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes. The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

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.

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.

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.

Deficit schizophrenia and its features are associated with PON1 Q192R genotypes and lowered paraoxonase 1 (PON1) enzymatic activity: effects on bacterial translocation.

Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured. DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

Frequency of Human Paraoxonase-1 Q192R Polymorphism and Measurement of Oxidative Stress Parameters in Infants with G6PD Deficiency

Background and Aims: This study aimed to investigate the frequency of Q192R polymorphism and oxidative stress markers in infants with glucose-6phosphate dehydrogenase (G6PD) deficiency. Materials and Methods: This is a case-control study in which 60 male infants (2-4 months old) with G6PD deficiency along with 60 age- and sexmatched healthy neonates were included. The diagnosis of G6PD deficiency was made by Beutler test by which the G6PD enzyme activity is measured by the fluorescent spot test. The blood samples were taken from all infants, and the sera were isolated for the evaluation of Paraoxonase-1 (PON1) and malondialdehyde (MDA) using the spectrophotometric method. Restriction fragment length polymorphism was applied for determination of Q192R polymorphism (rs 662). Results: The frequencies of QQ, QR, and RR genotypes were 55%, 39%, and 6%, respectively in infants with G6PD deficiency while the above genotype frequencies were 45%, 49%, and 6%, respectively in healthy neonates. The frequency of R and T alleles failed to show any significant difference when G6PD deficient infants and healthy neonates were compared. The results indicated PON1 activity and MDA levels being significantly (p&lt;0.05) higher in neonates with G6PD deficiency compared with their healthy counterparts. Conclusion: Contrary to previous studies, it was indicated that the presence of RQ and RR genotypes at Q192R position is associated with decreased activity of PON1 and increased oxidative stress. In this study, no significant differences were found in the genotype and allele frequency of PON1 Q192R polymorphism between the case and control groups. Also, this frequency was not consistent with the results obtained from oxidative stress conditions.

Paraoxonase 1 (PON1) L55M and Q192R Polymorphisms are Associated with Type 2 Diabetes Mellitus in Southern Thai Subjects

Background: Paraoxonase 1 (PON1) plays a critical role in the prevention of cardiovascular disease, diabetes mellitus, and other chronic diseases. Objective: The aim of the present study was to investigate the association of PON1 L55M and Q192R polymorphisms with type 2 diabetes mellitus (T2DM), and pre-diabetes. Materials and Methods: The present study included 512 subjects (223 T2DM patients, 150 pre-diabetes, and 139 healthy controls) from Southern Thailand. The PON1 L55M and Q192R polymorphisms were analyzed by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) technique. Results: PON1 Q192R polymorphism showed a statistical difference in genotype frequencies between T2DM patients and healthy controls (p&lt;0.0001). Multiple logistic regression analyses after adjusting for age, gender, and BMI showed that LM and RR genotypes increased the risk for T2DM compared with LL and QQ+QR genotypes (OR 1.96; 95% CI 1.02 to 3.76, p=0.042, and OR 1.85; 95% CI 1.11 to 3.10, p=0.019, respectively). Whereas, QR, genotype was associated with decreased risk for T2DM (OR 0.240; 95% CI 0.13 to 0.45, p&lt;0.0001), and pre-diabetes (OR 0.549; 95% CI 0.30 to 0.99, p=0.048) compared with QQ genotype. Conclusion: PON1 LM and RR genotypes may be genetic risk factors for developing T2DM but QR genotype may prevent T2DM, and pre-diabetes in Southern Thai population. Keywords: PON1, Polymorphisms, Type 2 diabetes, Pre-diabetes

Koroner Arter Hastalığında Paraoksonaz1 Q192R Polimorfizminin Rolünün Değerlendirilmesi

Koroner Arter Hastalığında Paraoksonaz1 Q192R Polimorfizminin Rolünün Değerlendirilmesi

Examination of Paraoxonase 1 Gene Polymorphism in Cases with Chronic Otitis Media

Objective: Chronic otitis media (COM) is a multifactorial disorder, the pathogenesis of which has yet to be fully elucidated. Numerous aetiological factors, including genetics, eustachian tube dysfunction, autoimmunity, infection, osteoclastic activity, cytokines, endotoxins, and products of lipid peroxidation resulting from oxidative stress, have been proposed to explain the chronic inflammation which lies at the heart of the disorder. The aim of this study is to investigate a possible relationship between the pathogenesis of COM and polymorphism within the paraoxonase 1 (PON1) gene. Methods: We investigated 49 patients admitted to the Otorhinolaryngology Department and diagnosed with COM between September and November 2017. The control group consisted of 51 healthy individuals. Polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) methods were used to genotype the PON1 Q192R (rs662) polymorphism. Results: When the case and control groups were compared in terms of the existence of PON1 (Q192) polymorphism, there was no statistically significant difference between the groups (p=0.166, p>0.05). When intergroup comparison was performed on the type of PON1 (Q192) polymorphism, there was also no statistically significant difference (p=0.261, p>0.05). Conclusion: The present study is the first known study in which PON1 polymorphism has been examined in cases of COM. The results of our study failed to indicate a statistically significant relationship between PON1 polymorphism and COM. However, it is important to note that the higher rate of 192RR polymorphism within the control group control may indicate a protective effect in COM.

Association of Serum Paraoxonase 1 Activities, Polymorphisms and Oxidative Stress in Breast Cancer Patients with Type 2 Diabetes Mellitus.

SummaryBackgroundThe aim of the study was to investigate the association of paraoxonase 1 (PON1) polymorphism, PON1/arylesterase (ARE) activity and oxidative stress index (OSI) in breast cancer (BC) patients with type 2 diabetes (DM).MethodsOur study group consisted of 30 healthy women (HV group) and 66 female BC patients. The BC patients were divided into two groups: those with (n=37) and without DM (n=29) (BDM and NBDM group). Genotyping of PON1 Q192R and L55M polymorphisms were done by polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) method. Serum PON1/ARE enzyme activities, total oxidant status (TOS) and total antioxidant status (TAS) were analysed by spectrophotometric method. The ratio of TOS to TAS was accepted as the oxidative stress index (OSI).ResultsPON1 Q192R genotype frequency distribution was significantly different in the BDM group compared to the NBDM group (p=0.021). When alleles distribution was examined, R and L alleles were significantly lower, Q and M alleles were significantly higher in the BDM group than in the NBDM group (p<0.001). TOS and OSI were statistically higher in BC patients than HV group (p<0.001).ConclusionsOur results suggest that PON1 gene Q and M alleles may be the risk factors predisposing formation of BC due to increased oxidant damage seen in DM. However, these statements require further confirmation with screening PON1 polymorphism in a greater number of patients with DM, and also wide range follow-up studies are necessary for the same purpose.

Paraoxonase 1 gene (Q192R) polymorphism confers susceptibility to coronary artery disease in type 2 diabetes patients: Evidence from case-control studies.

Numerous published studies have investigated the relationship between the paraoxonase 1 (PON1) gene Q192R (rs662) polymorphism and the risk of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. However, the results are still conflicting and inconclusive. Potentially eligible articles were searched for in related databases. Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the associations. Subgroup analysis was performed based on ethnicity. Ten case-control studies were included. A significant increase in the susceptibility for CAD in T2DM patients was found in the allelic model (OR = 1.49, p < 0.001), homozygote model (OR = 2.47, p < 0.001), heterozygote model (OR = 1.47, p < 0.001), dominant model (OR = 1.64, p < 0.001), and recessive model (OR = 1.74, p = 0.001). In subgroup analysis by ethnicity, a significant increase susceptibility was found in Asian populations in the allelic model (OR = 1.39, p = 0.001), homozygote model (OR = 2.15, p = 0.002), heterozygote model (OR = 1.37, p = 0.006), recessive model (OR = 1.65, p = 0.012), and dominant model (OR = 1.54, p < 0.001). A similar significant increase in susceptibility was found in Caucasian populations in the allelic model (OR = 1.75, p = 0.002), homozygote model (OR = 3.39, p = 0.002), recessive model (OR = 1.98, p = 0.030), heterozygote model (OR = 1.64, p = 0.001), and dominant model (OR = 1.83, p < 0.001). The results suggest that the PON1 Q192R polymorphism is associated with a significantly increased risk of CAD in T2DM patients in both Asian and Caucasian populations.