Association Between PON1 (L55M and Q192R) Genetic Polymorphism and Recurrent Pregnancy Loss in North Indian Women Exposed to Pesticides

Objective The aim of the present study was to examine the relation between the PON1 polymorphisms and recurrent pregnancy loss (RPL). Methods In a cross-sectional study, blood samples were collected from 100 females. DNA was extracted and PON1 genotypes were determined by polymerase chain reaction (PCR) amplification. Results Regarding PON1 L55M, the mutated allele (M) frequency was found in 70.5% in RPL and in 53.5% in controls; the M allele was significantly associated with an increased risk of RPL (adjusted odds ratio [ORadj] = 2.07; 95% confidence interval [CI]; p < 0.001). However, regarding PON1 Q192R, the R mutated allele frequency was found in 28.5% in RPL and in 33% in controls. The R allele did not show any risk for RPL (ORadj 0.81; 95%CI; p = 0.329). Conclusion The present study suggests that there is an effect of genetic polymorphism on RPL and provides additional evidence that combines with the growing information about the ways in which certain PON1 genotypes can affect the development of the fetus in the uterus.

PON1 polymorphisms can predict generalized anxiety and depressed mood in patients with multiple chemical sensitivity

Background: Multiple chemical sensitivity (MCS) is a chronic condition with somatic, cognitive and affective symptoms that follow contact with chemical agents at usually non toxic concentrations. We aimed to assess the role of genetic polymorphisms involved in oxidative stress on anxiety and depression in MCS. Materials & methods: Our study investigated the CAT rs1001179, MPO rs2333227, PON1 rs662 and PON1 rs705379 polymorphisms in MCS. Results: The AG genotype of the PON1 rs662 and the TT and CT genotypes of the PON1 rs705379 were involved in anxiety and depression. Discussion: These results are in line with existing evidence of PON1 involvement in MCS and suggest a further role of this gene in the exhibition of anxiety and depression in this disease.

Association of PON1 gene polymorphisms and enzymatic activity with risk of coronary artery disease

Background: The present case–control study evaluated the association of PON1 gene polymorphisms and enzyme activity in the western Indian population. Materials & methods: Angiographically proven coronary artery disease (CAD) formed the cases. PON1 polymorphisms (Q192R, L55M) and enzymatic activity (paraoxonase) were assessed. Results: A total of 502 participants (251 per group) were studied. PON1 Q192R and L55M polymorphisms were not associated with the risk of CAD. Notably, a weak association was observed between Q192R polymorphisms and the risk of CAD. CAD patients had significantly lower PON1 enzymatic activity (U/L) as compared with the controls regardless of the genotype. Conclusion: Low serum PON1 activity was confirmed to be an independent predictor for the risk of CAD.

P1275PARAOXONASE 1 (PON1) GENE POLYMORPHISMS, PON1 EXPRESSION IN PBMCS, AND SERUM PON1 ACTIVITY CONCERNING DYSLIPIDEMIA AND RELATED COMORBIDITIES IN HEMODIALYSIS (HD) PATIENTS

Background and Aims PON1 may prevent atherosclerosis influencing lipid metabolism and exerting antioxidant and anti-inflammatory activities. We focused on serum PON1 activity in HD patients concerning dyslipidemia, coronary heart disease (CHD), myocardial infarction (MI), and cerebral stroke (CS). PON1 activity was related to PON1 polymorphisms, PON1 expression in PBMCs, and demographic, clinical, and laboratory data. Method In 93 HD patients (men 55, age 66.7, 18.3 – 86.2 years, renal replacement therapy duration 3.9, 0.2 – 22.3 years, CHD 25, MI 15, CS 9), dyslipidemia was diagnosed by K/DOQI guidelines. The TG/HDL-cholesterol ratio of ≥3.8 indicated atherogenic dyslipidemia. Standard diagnostic rules were applied for CHD, MI, and CS recognition. PON1 activity was measured in serum using an automated PON1 assay kit. PON1 polymorphisms were genotyped by high-resolution melting curve analysis (rs662) or using predesigned TaqMan SNV Genotyping Assay (rs854560 and rs705379). In 46 subjects, the relative PON1 transcript level was determined in PBMCs using reverse transcription-quantitative polymerase chain reaction analysis. Results In univariate analyses, the lower serum PON1 activity the higher frequency of mixed dyslipidemia (LDL ≥ 100 mg/dL, TG ≥ 200 mg/dL, non-HDL ≥ 130 mg/dl; β ± SE: -21.4 ± 10.0, P = 0.035) and the higher serum TG levels (β ± SE: -1.06 ± 0.49, P = 0.034). Normalized serum PON1 activity (the PON1/HDL ratio) correlated positively with male sex (β ± SE: 0.56 ± 0.25, P = 0.029), atherogenic dyslipidemia (β ± SE: 0.67 ± 0.25, P = 0.008), and cigarette smoking (β ± SE: 0.86 ± 0.42, P = 0.043). After adjustment for gender, cigarette smoking, urine output, living in rural area, and serum phosphorus, significance was maintained between normalized serum PON1 activity and atherogenic dyslipidemia (β ± SE: 0.54 ± 0.24, P = 0.028), male sex (β ± SE: 0.51 ± 0.24, P = 0.037) and cigarette smoking (β ± SE: 0.93±0.41, P = 0.024) as well as revealed for living in rural area (β ± SE: 0.55 ± 0.26, P = 0.039), urine output (β ± SE: -0.14 ± 0.07, P = 0.046), and zinc supplementation (β ± SE: 1.5 ± 0.67, P = 0.029). PON1 activity (101, 27.7 – 213 U/L) and normalized PON1 activity (2.27, 0.57 – 7.10) were not influenced by PON1 polymorphisms and did not yield differences in patients stratified by CHD, MI, CS, and dyslipidemic patterns except atherogenic dyslipidemia. The latter relationship was caused by a correlation between serum PON1 activity and TG (r = -0.220, P = 0.034). PON1 transcript was detected in PBMCs of 9 subjects. They showed a higher prevalence of the AG + GG genotypes of PON1 rs662 (77.8% vs. 34.3%, P = 0.027), a higher serum CRP level (7.8, 2.8 – 46.8 mg/L vs. 3.9, 0.4 – 23.0 mg/L, P = 0.042), and a lower albumin (3.9, 2.6 – 4.5 g/dL vs. 4.2, 3.2 – 4.6 g/dL, P = 0.025) compared with the results of 37 subjects without the PON1 expression. The relative PON1 transcript level did not correlate with serum PON1 activity (r = 0.042, P = 0.915). Conclusion In HD patients, serum PON1 activity is associated with atherogenic dyslipidemia but not with already developed CHD and history of MI or CS, even after adjustment for several confounding variables. Illegitimate PON1 transcription occurs in uremic PBMCs at very low level and is influenced by PON1 rs662 polymorphism and upregulated by inflammation. PON1 could be considered as a therapeutic target in prevention of atherosclerosis and its complications in uremic patients.

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<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<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