title: Synergistic effects of BuChE non-UU phenotype and paraoxonase (PON1) 55 M allele on the risk of systemic lupus erythematosus: influence on lipid and lipoprotein metabolism and oxidative stress, preliminary report.
abstract: 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.
authors.affiliation: 1Molecular Diagnostic Research Center; Fertility and Infertility Research Center; Department of Clinical Biochemistry; Molecular Biology Research Center, Kermanshah University of Medical Sciences, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Bahrehmand
authors.forename: A
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.forename: Z
authors.initials: Z
authors.lastname: Rahimi
authors.forename: R
authors.initials: R
authors.lastname: Ahmadi
authors.forename: A
authors.initials: A
authors.lastname: Kiani
authors.forename: H
authors.initials: H
authors.lastname: Tavilani
authors.forename: H
authors.initials: H
authors.lastname: Vaisi-Raygani
authors.forename: T
authors.initials: T
authors.lastname: Pourmotabbed
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002091:Butyrylcholinesterase / Q000097:blood*; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D015227:Lipid Peroxidation; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D018384:Oxidative Stress; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D008315:Malondialdehyde; D019798:Neopterin; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Butyrylcholinesterase (BuChE) activity and phenotype; arylesterase activity; oxidative stress; paraoxonase (PON1) 55 polymorphism; systemic lupus erythematosus (SLE)