title: Association between butyrylcholinesterase activity and phenotypes, paraoxonase192 rs662 gene polymorphism and their enzymatic activity with severity of rheumatoid arthritis: correlation with systemic inflammatory markers and oxidative stress, preliminary report.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Shahmohamadnejad
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran; Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: asadvaisiraygani@kums.ac.ir.
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.affiliation: Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Yadola
authors.initials: Y
authors.lastname: Shakiba
authors.affiliation: Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Kiani
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Fariborz
authors.initials: F
authors.lastname: Bahrehmand
authors.affiliation: Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Ebrahimi
authors.initials: E
authors.lastname: Shakiba
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Tayehbeh
authors.initials: T
authors.lastname: Pourmotabbed
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002091:Butyrylcholinesterase / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007492:Iran; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018384:Oxidative Stress; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Anti-cytroline circulated peptide (CCP); Butyrylcholinesterase; Neopterin; Paraoxonase1-192rs662; Rheumatoid arthritis; Score of 28 joints (DAS28-CRP) of RA