title: Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High-Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease.
abstract: Paraoxonase 1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme that plays an important role in HDL-mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti-HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti-HDL antibodies, and CVD according to PON1 genetic variants in patients with RA.
  
  
  
  Serum PON-1 activity, using paraoxon as substrate, and IgG anti-HDL antibodies were quantified in 212 RA patients and 110 healthy controls. The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologics-naive patients with RA was prospectively followed up for 3 months.
  
  
  
  PON-1 activity was decreased in RA patients compared to healthy controls (P = 0.005), and an effect of the rs662 genotype was noted in both groups, with Q/Q homozygotes exhibiting the lowest PON-1 activity. The distribution of rs662 genotypes did not differ between RA patients and healthy controls (P = 0.215). In patients carrying the Q/Q genotype, anti-HDL antibodies were associated with impaired PON-1 activity (P = 0.010), and levels of anti-HDL antibodies were associated with decreased HDL levels (r = -0.680, P < 0.001) and higher prevalence of cardiovascular events, as determined in univariate and multivariate models. Furthermore, change in anti-HDL antibody levels upon tumor necrosis factor blockade was an independent predictor of improved PON-1 activity (β = -0.369, 95% confidence interval -0.669, -0.069; P = 0.024).
  
  
  
  PON-1 activity is impaired in RA in association with the rs662 genotype and anti-HDL antibodies, the latter being recognized as a pivotal player in the link between rs662 and CVD in patients with RA.
authors.affiliation: University of Oviedo, Asturias, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Mejías
authors.affiliation: Hospital Universitario Central de Asturias, Asturias, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alperi-López
authors.affiliation: University of Oviedo, Asturias, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Hospital Universitario Central de Asturias, Asturias, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ballina-García
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Santander, Spain, and Clinical University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Miguel Á
authors.initials: MÁ
authors.lastname: González-Gay
authors.affiliation: University of Oviedo, Asturias, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D043303:Aryldialkylphosphatase / Q000502:physiology*; D001323:Autoantibodies / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase