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Rheumatoid arthritis (RA) is considered as a long-term autoimmune disorder. Gene polymorphism and oxidative stress might be involved in the pathogenesis of the disease. We aimed to determine the association between PON-1L55M polymorphism and its effects on inflammatory markers such as anti-cytroline circulated-peptide (CCP)-antibodies, C-reactive protein (CRP), neopterin serum concentration, arylesterase (ARE) and butyrylcholinesterase (BuChE) activities and total-antioxidant-capacity (TAC) level with the activity of disease in RA patients. This case-control study consisted of 419 RA patients and 397 gender-age-matched unrelated healthy controls from the west of Iran. PON1-L55M polymorphism was detected by real-time-PCR. The TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. The PON1-M55 allele was associated with increased risk of the RA in cases with moderate or high activity (OR = 1.43, p = 0.023) and also in cases with the presence of anti-CCP antibody (OR = 1.51, p = 0.009). Synergistic effects of PON1 M55 and Q192 alleles resulted in 2.14 times (p = 0.021) increased disease activity among RA patients with moderate or high activity of the disease. RA patients carried both M (PON1 L55M) and Q alleles (PON1Q192R) had higher concentrations of neopterin (p = 0.003), anti-CCP-antibody (p < 0.001) and CRP (p = 0.026) and significantly lower TAC level (p < 0.001) and ARE (p < 0.001) activity compared to controls. The current study suggests there might be a relationship between genetic and activity of PON. Also, the PON1L55M and PON1Q192R could act in synergy to increase the risk of RA and enhance the level of oxidative stress markers.

Evidences indicate that abnormal lipid metabolism and lipid peroxidation can affect the progression of complications in systemic lupus erythematosus (SLE) patients. Apolipoprotein E (ApoE) and paraoxonase-1 (PON1) play important role in lipid metabolism and protection of lipid peroxidation. The polymorphisms of ApoE and paraoxonase (PON1) L55M (Met < Leu) allele genes lead to disorders in lipid metabolism and are related to atherosclerosis. This study is the first investigation to examine the possible association between ApoE and PON1-L55M polymorphisms and correlation with serum arylesterase (ARE) activities of PON, levels of malondialdehyde (MDA), neopterin, and lipid lipoprotein in SLE patients from Iranian western population. The present case-control study consisted of 107 SLE patients and 101 gender- and age-matched, unrelated, healthy controls from Iran's western population. The ApoE and PON1-L55M genotypes were identified using PCR-RFLP method. The serum level of MDA, neopterin, lipid levels, and ARE activity were determined by HPLC, commercial kits, and spectrophotometry, respectively. Our results showed that ApoE ε4 and PON1-55M alleles act synergistically to increase the risk of SLE by 1.47 times (p = 0.038). We found that the frequency of ApoE Ɛ3/Ɛ4 genotype was higher in SLE patients (11.2%) compared with control subjects (5%), although the difference was not significant (p = 0.087). This study for the first time not only demonstrates that ApoE Ɛ4 and PON-55M alleles synergistically increase the risk of SLE but also reveals that serum levels of MDA, neopterin, and LDL-C are high in SLE patients. This information may be in value for evaluating SLE progression and in the elucidation of the mechanisms of the disease pathogenesis.

Objectives: Evidences indicate that oxidative stress and inflammation are important processes in the development of destructive synovial tissue in rheumatoid arthritis (RA). The two major bioscavenger enzymes that are associated with inflammation and oxidative stress are human-butyrylcholinesterase (BuChE) and paraoxonase-1 (PON-1). Thus, the objective of this study was to determine the relation of BuChE phenotypes and PON-1 Q192R polymorphism with inflammatory markers such as anti-cytroline circulated peptide (CCP)-antibodies, CRP, neopterin, DAS28-CRP in RA patients., Design and Methods: In this study, we examined association of BuChE-phenotypes and activity, PON192rs662 (Q192R) polymorphism and its arylesterase activity (ARE) with systemic-inflammatory-markers and oxidative stress. The present case-control study consisted of 419-RA patients and 398 gender-age-matched unrelated healthy controls from west population of Iran. PON192rs662 polymorphism was detected by real-time-PCR. BuChE phenotype, TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. We used the EULAR activity criteria to measure DAS28-CRP., Results: We found that PON-1-Q192R was associated with severity of RA [remission-to-low and moderate-to-high in dominant Q/Q+Q/R vs. R/R: OR=2.27, p<0.001; codominant Q/Q vs. R/R: OR=1.65, p<0.001 and Q/R vs. R/R: OR=2.12, p=0.003; recessive Q/Q vs. R/R+Q/R: OR=1.79, p=0.032; and allele Q vs. R: OR=1.68, p<0.001] and presence of anti-CCP-antibody (codominant model Q/Q vs. R/R: OR=1.28, p=0.042). The carriers of Q/Q genotype PON-1-Q192R and BuChE non-UU-phenotype had higher ARE activity, serum levels of neopterin, anti-CCP antibody titer and number of tender-joint and lower activity of BuChE and serum level of TAC than that of R/R genotype and BuChE-UU-phenotype., Conclusions: The current findings demonstrate for the first time that there is a link between systemic inflammatory markers, oxidative stress, the PON192rs662-Q allele and BuChE-non-UU-phenotype and their corresponding enzymatic activity which may be considered as a risk factor for the severity of RA for a population in Iran., (Copyright © 2014 The Canadian Society of Clinical Chemists. All rights reserved.)

There is some evidence indicating lipid peroxidation can affect progression of atherosclerosis, cardiovascular diseases (CVDs) and glomerulonephritis in systemic lupus erythematosus (SLE) patients. Human butyrylcholinesterase (BuChE) and paraoxonase-1 (PON1) are two major bioscavenger enzymes that are associated with inflammation, oxidative stress and lipid metabolism. Hyperlipidemia, increase in lipid oxidation reactions and defects in antioxidant status may lead to increased oxidative stress and high frequency of CVDs in SLE. It has also been suggested that deficiency in the function of the antioxidant system and an increase in reactive oxygen release (ROS) may play an important role in the pathogenesis of SLE. This study is the first investigation to examine the association of BuChE phenotypes, PON1 (L55M; PON-55-M) polymorphism, the levels of malondialdehyde (MDA), neopterin, lipid-lipoprotein and activities of BuChE and arylesterase activity (ARE) of PON with severity of SLE. The present case-control study consisted of 109 SLE patients and 101 gender- and age-matched, unrelated healthy control subjects from the population of west Iran. We found that the PON-55-M allele and BuChE non-UU act synergistically to increase the risk of SLE by 2.5 times (1.03-6.7, p = 0.044). There was a significant negative correlation between severity of SLE with serum BuChE activity (R = -0.31, p < 0.001) and positive correlation with serum neopterin level. The SLE patients with the PON-55-M (M/L + M/M) allele or with BuChE non-UU phenotype had significantly lower serum ARE and BuChE activities than those with PON-55-L/L or BuChE-UU phenotypes, respectively. In addition, their serum levels of MDA, neopterin and LDL-C were significantly elevated, suggesting that these individuals are more susceptible to CVD. However, further studies are needed to shed more light on the contribution of the M allele of PON1 and non-UU phenotypes of BuChE in the development of SLE in different ethnicities.

Paraoxonase-1 (PON1) is a serum HDL-bound enzyme that hydrolyzes a number of aromatic carboxylic acid esters including lipid peroxides, preventing LDL oxidation. Systemic lupus erythematosus (SLE) patients are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism. In this study, association of PON-55 polymorphism with serum arylesterase (ARE) activities, malondialdehyde (MDA), neopterin, lipids and lipoproteins levels in SLE patients and the development of hypertension was investigated. The present case-control study consisted of 109 SLE patients with and without high blood pressure (BP) and 103 healthy controls from the population in the west of Iran. PON-55 Met&lt;Leu polymorphism was detected by restriction fragment length polymorphism (PCR-RFLP), serum ARE activity, MDA, neoptrin, lipid and apolipoprotein levels were determined by spectrophotometery and HPLC and enzyme assay, respectively. The presence of PON-55 M/M genotype was found to be associated with SLE and the development of high BP. The SLE patients with PON-M (M/L+M/M) allele had significantly lower serum ARE activity, but higher neoptrin and LDL-C than the carriers of corresponding genotypes in control group. The ARE activity was positively correlated with HDL-C and negatively correlated with LDL-C and MDA levels in SLE patients. Whereas, in SLE patients with high BP, ARE activity was only found to be negatively correlated with MDA concentration. These data suggest that PON-55 M/M genotype is a risk factor for SLE. The carriers of this allele have high levels of MDA, neopterin and LDL-C, thus, they are more likely to develop hypertension.

Background: Paraoxonase 1 (PON1) is a serum high-density lipoprotein-bound enzyme with antioxidant function. It hydrolyses lipid peroxides, protecting low-density lipoproteins from oxidative modifications. Patients with psoriasis are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism., Objectives: In this study, association of the PON1 55 M allele with serum arylesterase (ARE) activity, malondialdehyde (MDA), lipid profiles and psoriasis was investigated., Methods: The present case-control study consisted of 100 patients with psoriasis with and without cardiovascular diseases (mean age 35·3 years) and 100 sex- and age-matched unrelated healthy controls (mean age 35·7 years) from the population of western Iran. The PON1 55 Met>Leu polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. Serum ARE activity, MDA, and lipid and apolipoprotein levels were determined spectrophotometrically, by high-performance liquid chromatography and by enzyme assay, respectively., Results: The presence of the PON1 55 M allele was found to be associated with psoriasis (odds ratio = 1·96, P = 0·017). The patients with psoriasis with the PON1 M (M/L + M/M) allele had higher MDA levels (4·12 ± 0·88 vs. 2·24 ± 0·55 μmol L(-1) , P < 0·001), apolipoprotein B (APOB)/APOA1 ratio (0·91 ± 0·66 vs. 0·66 ± 0·35, P = 0·004), APOB (111 ± 38·7 vs. 88·3 ± 22·5 mg mL(-1) , P = 0·001) and lipoprotein(a) [LP(a)] (21·9 ± 18·4 vs. 15·8 ± 16·6 mg mL(-1) , P = 0·034), but lower ARE activity (39·6 ± 11 vs. 45·9 ± 11·8 U mL(-1) , P = 0·031) than the control subjects. ARE activity showed a significant positive correlation with APOA1 and a negative correlation with MDA concentration in patients with psoriasis., Conclusions: The PON1 55 M allele is a risk factor for psoriasis. Carriers of this allele have high levels of MDA, APOB and LP(a), a high APOB/APOA1 ratio and low ARE activity. These results indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of psoriasis and its related complications. These data suggest that patients with psoriasis are more susceptible to vascular diseases., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

We have previously shown that angiotensin-converting enzyme (ACE) gene D allele is an independent risk factor for early onset coronary artery disease (CAD). Little is known about the concomitant presence of the ACE gene D allele and paraoxonase (PON1) codon 192 arginine (Arg) on the severity of CAD. Regarding the high rate of CAD among Iranians the aim of present study was to examine the hypothesis of synergistic effects between ACE-D and PON1-Arg alleles on predisposition and the severity of CAD in our population. The PON1 192 and ACE insertion/deletion (I/D) genotypes were detected by PCR-RFLP and PCR, respectively in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control without CAD or diabetes. We mentioned the synergistic effects of both genes and not ACE gene alone is a risk factor for CAD. We found that PON1 Arg 192 and ACE D allele act synergistically to increase the risk of CAD (OR 1.3, P = 0.044). Our results showed a significant correlation between the possession of both PON1 192 Arg and the ACE D allele and the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel disease with OR 2.7, P = 0.046; χ(2) = 4, P = 0.046 and OR 2.4, P = 0.051; χ(2) = 3.8, P = 0.051, respectively. We found that PON1 Arg 192 and ACE D alleles act synergistically to increase the risk of CAD in CAD patients and CAD subjects without diabetes from west of Iran, who have high frequency of three-vessel disease. Our data suggest that PON1 192 Arg and the ACE D allele in combination with each other can be important independent risk factor for severity of CAD in patients carrying both PON1 192 Arg and the ACE D allele in a west population of Iran.

The role of the paraoxonase (PON1) codon 192 polymorphism [glutamine (Q)/arginine (R)] in coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate whether the PON1 gene polymorphism is an independent risk factor for severity of coronary artery disease in patients from west of Iran. The PON1-Arg-192 genotypes were detected by PCR-RFLP in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control without CAD or diabetes. The frequency of PON1-Arg-192 allele was significantly higher in the CAD (23.4 vs. 16%, P = 0.032) than in the control group and there was a higher risk of developing CAD (OR = 1.6, P = 0.02). In addition, this difference remained significant after adjustment for without history of diabetes (OR = 1.47, P = 0.048), presence of normolipidemia and absence of history of blood pressure (OR = 1.4, P = 0.05). This result indicated PON1-Arg-192 allele is a risk factor of CAD also when correcting for conventional risk factors. We found a significant association between the PON1-Arg-192 genotype (QR + RR) and the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel disease with OR = 1.49, P = 0.046; χ2 = 3.82, P = 0.048 and OR = 1.46, P = 0.05; χ2 = 3.48, P = 0.051, respectively. The CAD patients carrying PON1-Arg-192 genotype (QR + RR) had lower plasma HDL-C level (P = 0.019) and higher plasma LDL-C(P = 0.01) and TG(P = 0.05). Our results indicated that PON1-Arg-192 allele can be important independent risk factor of CAD in a west population of Iran, with carriers of PON1-Arg-192 having an increased frequency of three-vessel disease and also having a distinct plasma lipids profile. Larger collaborative studies are needed to confirm these results.