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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.

Angiotensin II, one of the rennin-angiotensin system components, is important in the cardiovascular hemodynamic and plays an important role in the development of cardiovascular disease in systemic lupus erythematosus (SLE) patients. The angiotensin II, through interaction with angiotensin II type 1 receptor (AGTR1), promotes proliferation, inflammation and fibrosis. The single nucleotide polymorphism of the AGTR1 (dbSNP: rs5186) gene can be associated with development and progression of SLE disease. The aims of this study were to compare the frequency of AGTR1 rs5186 in SLE patients with healthy individuals and to evaluate possible association between AGTR1 A1166C gene polymorphism and serum level of lipids, neopterin and malondialdehyde in SLE patients from a population of West Iran. One hundred SLE patients and 98 healthy subjects were studied. The AGTR1 A1166C polymorphism was detected by polymerase chain reaction- restriction fragment length polymorphism method and the serum lipid profile was obtained by enzymatic method. Neopterin and malondialdehyde were detected using high-performance liquid chromatography. We did not detect significant association between AGTR1 A1166C polymorphism and the risk of SLE. The levels of triglyceride (225 ± 118 mg/dl), neopterin (30 ± 24 nmol/l) and malondialdehyde (25 ± 9.6 nmol/l) in SLE patients were significantly higher than those in control subjects (139 ± 56 mg/dl, p = 0.03, 6.4 ± 2, p = 0.03, 9.4 ± 2.5 nmol/l, p = 0.01, respectively). Individuals with AGTR1 AC + CC genotype had higher levels of total cholesterol and malondialdehyde compared with those with AGTR1 AA genotype. SLE patients with either AGTR1 AA or AGTR1AC + CC genotype had significantly higher malondialdehyde or neopterin levels compared with the corresponding control subjects. In conclusion, although the present study did not find any association between AGTR1 A1166C polymorphism and the risk of SLE, the presence of this polymorphism was associated with higher levels of malondialdehyde and higher concentration of neopterin in patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs and is characterized by persistent systemic inflammation. Among the effects of inflammatory mediators, the induction of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and oxidative stress has been demonstrated to be important in the development of SLE. In this study, the possible association between MMP-9 and MMP-2 functional promoter polymorphism, stress, and inflammatory markers with development of severe cardiovascular disease (CVD), high blood pressure (HBP), and lupus nephropathy (LN) in SLE patients was investigated. The present case-control study consisted of 109 SLE patients with and without CVD, HBP and LN and 101 gender- and age-matched unrelated healthy controls from a population in western Iran. MMP-2 -G1575A and MMP-9 -C1562T polymorphisms were detected by PCR-RFLP, serum MMP-2 and MMP-9, neopterin, malondialdehyde (MDA) and lipid levels were determined by ELISA, HPLC and enzyme assay, respectively. We found that MMP-9 -C1562 T and MMP-2 -G1575A alleles act synergistically to increase the risk of SLE by 2.98 times (p = 0.015). Findings of this study also demonstrated that there is a significant increase in the serum levels of MMP-2, neopterin and MDA and a significant decrease in serum level of MMP-9 in the presence of MMP-9-C1562 T and MMP-2 -G1575A alleles in SLE patients compared to controls. Further, SLE patients with MMP-9 (C/T + T/T) genotype had significantly higher serum concentrations of MMP-2, neopterin, MDA and LDL-C, but lower serum MMP-9 and HDL-C levels than corresponding members of the control group. MMP-9 (C/T + T/T) genotype increased risk of hypertension in SLE patients 2.71-fold. This study for the first time not only suggests that MMP-9 -C1562 T and MMP-2 -G1575A alleles synergistically increase the risk of SLE but also high serum levels of MDA, neopterin, and circulatory levels of MMP-2 and lower MMP-9 in SLE patients. This information may be important in the evaluation of SLE progression and in the elucidation of the mechanisms of the disease pathogenesis., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

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.)

Background: Psoriatic patients are at greater risk of oxidative stress and inflammation which is associated with abnormal plasma lipid metabolism and lipid peroxidation.There is not any information about the clinical significance of relation between methylentetrahydrofolatereductase (MTHFR) 677-T allele with malondialdehyde (MDA), lipids, apolipoproteins and vascular adhesion protein-1 (VAP-1) partakes in the migration process of lymphocytes into sites of inflammation., Objectives: This study is the first investigation to examine the association of MTHFR (rs1801133) C677T polymorphism, serum level of MDA, VAP-1, lipid-lipoprotein and apolipoproteins with the risk of psoriasis., Methods: The present case-control study consisted of 100 psoriatic patients and 100 gender- and age-matched unrelated healthy controls from west population of Iran. MTHFR-C677T (rs1801133) polymorphisms were detected by restriction fragment length polymorphism (PCR-RFLP), VAP-1 by ELISA, apolipoproteins by immunoprecipitation, lipid and apolipoproteins by spectrophotometery and MDA by HPLC., Results: We found that dominant/recessive model (CC + CT/TT) and T allele of MTHFR-677 alleles significantly 7.45 and 1.76 times increased risk of psoriasis, respectively. The psoriasis patients with MTHFR-677-T (C/T + T/T) allele had significantly higher serum MDA, VAP-1 and apolipoproteinsAPOB concentrations and ratio of APOB/APOA1 than the control subjects.The MTHFR-677-T allele frequencies in psoriasis patients were significantly higher than that in control group (28.5% vs. 18.5%; P = 0.018).We found a significant positive correlation between VAP-1 with MDA (P = 0.047) and LP (a) (P = 0.025)., Conclusion: In the present study, we demonstrated for the first time that the psoriasis patients with MTHFR-677-T (C/T + T/T) allele had higher serum levels of MDA, VAP-1, APOB and ratio of APOB/APOA1 and dominant/recessive model (CC+CT/TT) and T allele of MTHFR-677 are significantly more common in psoriasis and increased risk of psoriasis by 7.45 and 1.76 fold, respectively. These data suggest that psoriasis patients carrying of TT genotypes and T allele of MTHFR-677 may be more susceptible to cardiovascular disease and myocardial infarction., (© 2013 European Academy of Dermatology and Venereology.)

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.

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. [ABSTRACT FROM AUTHOR]