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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.

We have previously shown that butyrylcholinesterase-K (BCHE-K, G1615A/Ala539Thr) variant increases the risk of coronary artery disease (CAD). In addition, we have found that the presence of APOE-epsilon 4 allele augments the risk of CAD in patients with type II diabetes mellitus (T2DM/CAD). Here we explored the concomitant presences of two alleles of the BCHE-K and APOE-epsilon 4 in increasing the risk of CAD or diabetes in T2DM patients with or without CAD and CAD patients without T2DM. This case-control study comprised 631 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: type II diabetic patients with no sign of CAD (T2DM), type II diabetic patients with CAD/ND (T2DM/CAD), CAD patients with no sign of diabetes (CAD/ND), and healthy individuals (NCAD/ND). BCHE-K variant and APOE genotypes were detected by PCR-RFLP and serum lipid level was measured enzymatically. We found that BCHE-K and APOE-epsilon 4 allele act synergistically to increase the risk of CAD in both T2DM, non-diabetic and total CAD (TCAD = T2DM/CAD + CAD/ND) individuals. The level of synergy 1.5 and 1.2 fold are higher in CAD patients (OR = 4.5; P = 0.011) with T2DM than the non-diabetic CAD patients (OR = 3.07; P = 0.024) and TCAD patients (OR = 3.74; P = 0.018), respectively. The CAD subjects with and without T2DM and TCAD patients carrying both APOE-epsilon 4 allele and BCHE-K had significantly lower plasma HDL-C (P values = 0.008, 0.047, and 0.036, respectively) and higher plasma LDL-C (P values = 0.025, 0.048, and 0.04, respectively), than that of the control carriers both APOE-epsilon 4 and BCHE-K. We have found that BCHE-K and APOE-epsilon 4 allele not only act synergistically to increase the risk of CAD, particularly in T2DM subjects in population from western Iran, who have high levels of LDL-C and low levels of HDL-C, suggesting that a specific therapeutic intervention should be considered for these particular groups of patients.

Background: Butyrylcholinesterase (BuChE) catalyzes the hydrolysis of acetylcholine and other choline esters and is also involved in lipid metabolism. The purpose of this study was to investigate any association between BuChE serum phenotype and activity and lipid profile of ischemic stroke patients., Methods: We determined serum BuChE activities and phenotypes, and levels of total cholesterol (TC), LDL-C, HDL-C and triacylglyerol (TG) in 33 patients with acute ischemic stroke within 12 h of the onset of the attack and 29 controls., Results: The mean (+/-SD) serum BuChE activity and the BuChE of U/A phenotype in the stroke individuals were significantly lower and higher than that of the control (315 (+/-124) IU/L. vs. 384 (+/-99) IU/L, p=0.02, t=-2.4 and 21.2% vs.3.4%, p=0.026 respectively)., Conclusions: Our results showed that a negative correlation between BuChE activity with TC level, in addition the frequency of BuChE phenotypes with low activity is high in stroke patients, who have high levels of cholesterol, may have increased susceptibility to stroke.

The conflicting results of several studies suggest that there is an association between the butyrylcholinesterase-K variant (BCHE-K, G1615A/Ala539Thr) and the risk of developing coronary artery disease (CAD) in diabetes and non-diabetic subjects. The objective of this study was to determine whether the presence of the BCHE-K variant exacerbates the risk of CAD in patients from western Iran with and without type 2 diabetes mellitus (T2DM). This case-control study comprised 464 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: CAD+T2DM+ (CAD/T2DM), CAD+DM(-) (CAD/ND), CAD(-)DM+ (T2DM/NCAD) and CAD(-)DM(-)(control). The BCHE-K variant was detected by PCR-RFLP. The BCHE-K allele frequency in CAD patients with and without T2DM [total CAD (TCAD)] and separately for each group (CAD/T2DM and CAD/ND) was significantly higher than in the control group (21.1 % versus 13.3 % (p = 0.001), 22.4 % versus 13.3 % (p = 0.001) and 19.7 % versus 13.3 % (p = 0.015), respectively). The odds ratios (ORs) for the BCHE-K heterozygous and homozygous variants in TCAD subjects were 1.65 (95 % CI 1.17-2.3; p = 0.004) and 4.3 (1.05-19.4; p = 0.048); for CAD/T2DM individuals 1.76 (1.2-2.6; p = 0.004) and 4.73 (0.96-23.3; p = 0.052); and for CAD/ND patients 1.53 (1.05-2.3; p = 0.029) and 3.88 (0.8-19.7; p = 0.7), respectively. The OR of the BCHE-K allele was found to be 1.74 (1.1-2.4; p = 0.001) in TCAD subjects, 1.87 (1.12-1.48; p = 0.001) in the CAD/T2DM group and 1.59 (1.04-1.4; p = 0.016) in CAD/ND subjects. These data suggest that the BCHE-K allele increases the risk of CAD in the population (with and without DM) in western parts of Iran, and its presence intensifies the risk of CAD in T2DM. The fact that the BCHE-K allele, even in the heterozygous form, exacerbates the risk of CAD in this population, suggests that a specific therapeutic intervention should be considered for this particular group of patients.

Objective: The best known clinical application of serum BChE assay is to predict abnormally prolonged apnea following the application of the muscle relaxant succinylcholine. The aim of the present study was to assess the frequency of BChE phenotypes and to predict the risk of apnea for those receiving succinylcholine among the residents in western Iran., Methods: We examined the frequency of nine BChE phenotypes in 1548 volunteers including 816 males and 732 females with the mean age of 35+/-15 years from an apparently healthy group living in western Iran. The frequencies of BChE phenotypes were determined using BChE activity measurements and by inhibition with dibucaine, fluoride, and the compound Ro2-0683 (Hoffman-La-Roche)., Results: The reference range for serum total BChE activity was 4600-14000 U/L (using butyrylthiocholine iodide as substrate). The mean value obtained for men (9030 U/L) was significantly (p<0.05) higher than that for women (8550 U/L). The frequencies of four alleles U, A, F, S were calculated to be 0.9826, 0.0165, 0.008 and 0.001, respectively. The frequency of phenotypes of BChE was as follows: normal phenotype (UU) 95.5%, moderate sensitive to succinylcholine including UA,US,UF phenotypes was 3.9% and hypersensitive to succinylcholine (AA, AF, AS, FF, SS) was 0.58%., Conclusion: This study indicates that the population of western Iran has a medium frequency of succinylcholine-sensitive individuals compared to other populations. We suggest that determination of BChE activity and phenotype by the micro automated method is well suited to pre-operative screening and detection of at-risk of prolonged apnea in persons receiving succinylcholine in the healthy population of western Iran.

Recent studies indicate that there is a synergic association between butyrylcholinesterase-K variant (BChE-K) and apolipoproteinE-epsilon 4 (ApoE-epsilon 4) to promote risk for Alzheimer's disease (AD). Most subsequently replicative studies have been unable to confirm these finding. We attempted to replicate this finding in 105 AD cases and age and sex matched 129 controls from Tehran population, Iran. The BChE genotype of patients were found to be significantly different from controls (chi(2) = 12.2, d.f. = 2, p = 0.002). The frequency of BChE-K allele was also found to differ significantly in cases compared to controls [24% versus 12% (chi(2) = 20.6, d.f. = 2, p < 0.001)] leading to an increased risk of AD in subjects with this allele (OR = 2.5, 95% CI = 1.64-3.8, p = 0.001). This risk was found to increase from (OR = 2.37, 95% CI = 1.3-4.2, p = 0.006) in subjects less than 75 years old to (OR = 3.16, 95% CI = 1.41-7.1, p = 0.001) in subjects 75 years and older. But, the ApoE-epsilon 4 allele association risk was found to decrease from (OR = 9.5, 95% CI = 3.74-24.1, p = 0.001) in subjects <75 years to (OR = 1.36, 95% CI = 0.49-4.1, p = 0.58) in those subjects 75 years and older. Furthermore, we found a very strong synergic association between BChE-K and ApoE-epsilon 4 OR = 19.1 (95% CI = 428-85.45, p < 0.001). In spite of this, synergism decreased from OR = 36.2 (95% CI = 4.4-296, p = 0.001) in subjects <75 year olds to OR = 6.2 (95% CI = 0.9-72.4, p = 0.06) in subjects > or =75 years. We have found that BChE-K and ApoE-epsilon 4 alleles act synergistically to increase the risk of the late-onset AD, particularly in age group <75 years in Tehran, Iran.