Charles-Schoeman Christina, Lee Yuen Yin, Shahbazian Ani, Gorn Alan H, Fitzgerald John, Ranganath Veena K, Taylor Mihaela, Ragavendra Nagesh, McMahon Maureen, Elashoff David, Reddy Srinivasa T
David Geffen School of Medicine, University of California, Los Angeles.
Arthritis Rheum. 2013 Nov;65(11):2765-72. doi: 10.1002/art.38118.
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).
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.
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).
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.
探讨对氧磷酶1活性的遗传和生化决定因素与类风湿关节炎（RA）患者颈动脉斑块的关系，颈动脉斑块是心血管（CV）风险的替代标志物。
在168例RA患者中确定对氧磷酶1活性、PON1基因型（第192位功能性多态性）与颈动脉斑块存在情况之间的关系。空腹过夜后，采集血液进行脂蛋白分析，以对氧磷作为底物测量对氧磷酶1活性。测定所有患者的PON1 Q192R基因型。评估所有患者的脂蛋白胆固醇水平、传统CV危险因素、药物使用情况和RA疾病特征。
RA患者中，RR基因型的对氧磷酶1活性值最高，QR基因型次之，QQ基因型最低（P < 0.0001）。与QQ基因型或QR基因型患者相比，RR基因型患者在多变量分析中，在控制传统CV危险因素、高敏C反应蛋白水平、泼尼松使用情况和降胆固醇药物使用情况后，颈动脉斑块风险降低（P < 0.05）。控制上述因素的额外多变量logistic回归分析也显示，RA患者血浆对氧磷酶1活性与颈动脉斑块之间存在显著关联。血浆对氧磷酶1活性较低与颈动脉斑块风险增加相关（P < 0.05）。
目前的研究结果表明，通过颈动脉斑块的有无评估，对氧磷酶1的遗传决定因素和活性与RA患者的CV风险相关。有必要进行进一步的CV结局研究，以验证对氧磷酶1作为RA患者CV风险生物标志物的效用。
