title: Association of paraoxonase 1 gene polymorphism and enzyme activity with carotid plaque in rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients.
  
  
  RESULTS
  Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P < 0.0001). Compared to patients with either the QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased risk of carotid plaque on multivariate analysis, controlling for traditional CV risk factors, high-sensitivity C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (P < 0.05). Additional multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P < 0.05).
  
  
  CONCLUSIONS
  The current findings suggest a relationship of the genetic determinants and activity of paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: Christina
authors.initials: C
authors.lastname: Charles-Schoeman
authors.forename: Yuen Yin
authors.initials: YY
authors.lastname: Lee
authors.forename: Ani
authors.initials: A
authors.lastname: Shahbazian
authors.forename: Alan H
authors.initials: AH
authors.lastname: Gorn
authors.forename: John
authors.initials: J
authors.lastname: Fitzgerald
authors.forename: Veena K
authors.initials: VK
authors.lastname: Ranganath
authors.forename: Mihaela
authors.initials: M
authors.lastname: Taylor
authors.forename: Nagesh
authors.initials: N
authors.lastname: Ragavendra
authors.forename: Maureen
authors.initials: M
authors.lastname: McMahon
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D016893:Carotid Stenosis / Q000453:epidemiology* / Q000235:genetics*; D004789:Enzyme Activation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
references.citation: Life Sci. 2003 May 9;72(25):2877-85
references.pmid: 12697270
references.citation: Arthritis Rheum. 1980 Feb;23(2):137-45
references.pmid: 7362664
references.citation: N Engl J Med. 2012 Nov 29;367(22):2089-99
references.pmid: 23126252
references.citation: Arthritis Rheum. 2011 May;63(5):1211-20
references.pmid: 21305526
references.citation: J Rheumatol. 2007 Jul;34(7):1459-64
references.pmid: 17552046
references.citation: Arthritis Rheum. 2001 Dec;44(12):2737-45
references.pmid: 11762933
references.citation: Circulation. 2005 Mar 15;111(10):1313-20
references.pmid: 15769774
references.citation: Biochem Pharmacol. 2005 Feb 15;69(4):541-50
references.pmid: 15670573
references.citation: J Clin Invest. 1995 Feb;95(2):774-82
references.pmid: 7860760
references.citation: Annu Rev Med. 2003;54:371-92
references.pmid: 12525679
references.citation: Arthritis Rheum. 1995 Jan;38(1):44-8
references.pmid: 7818570
references.citation: Circulation. 2003 Mar 11;107(9):1303-7
references.pmid: 12628952
references.citation: J Rheumatol. 2007 May;34(5):937-42
references.pmid: 17361987
references.citation: N Engl J Med. 2007 Nov 22;357(21):2109-22
references.pmid: 17984165
references.citation: J Clin Invest. 1997 Apr 15;99(8):2005-19
references.pmid: 9109446
references.citation: J Lipid Res. 2000 Sep;41(9):1495-508
references.pmid: 10974057
references.citation: J Lipid Res. 2000 Sep;41(9):1481-94
references.pmid: 10974056
references.citation: Am J Cardiol. 2004 Jan 15;93(2):198-200
references.pmid: 14715346
references.citation: J Rheumatol. 2008 Mar;35(3):398-406
references.pmid: 18203326
references.citation: Arterioscler Thromb Vasc Biol. 2001 Apr;21(4):473-80
references.pmid: 11304460
references.citation: Arthritis Rheum. 2012 Jun;64(6):1828-37
references.pmid: 22231638
references.citation: Clin Rheumatol. 2007 Mar;26(3):342-8
references.pmid: 16642406
references.citation: J Clin Invest. 2006 Dec;116(12):3090-100
references.pmid: 17143322
references.citation: Ann Rheum Dis. 2012 Jul;71(7):1157-62
references.pmid: 22267330
references.citation: FEBS Lett. 1991 Jul 29;286(1-2):152-4
references.pmid: 1650712
references.citation: JAMA. 2008 Mar 19;299(11):1265-76
references.pmid: 18349088
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: Arthritis Rheum. 2009 Oct;60(10):2870-9
references.pmid: 19790070
references.citation: Ann Rheum Dis. 2009 Jun;68(6):868-72
references.pmid: 18635596