Tripi Laura M, Manzi Susan, Chen Qi, Kenney Margaret, Shaw Penny, Kao Amy, Bontempo Franklin, Kammerer Candace, Kamboh M Ilyas
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Arthritis Rheum. 2006 Jun;54(6):1928-39. doi: 10.1002/art.21889.
Low serum paraoxonase 1 (PON1) activity determined with paraoxon as substrate has been found to be associated with coronary artery disease. This study was undertaken to examine the relationship of PON1 activity and genotype to risk of systemic lupus erythematosus (SLE).
The impact of 7 PON1 single-nucleotide polymorphisms (SNPs) was analyzed in relation to PON1 activity, SLE risk, lupus nephritis, antiphospholipid antibody (aPL) positivity, and carotid vascular disease in 380 SLE patients (334 white, 46 black) and 497 controls (455 white, 42 black).
Compared with findings in controls, PON1 activity with paraoxon substrate was reduced both in white lupus patients (mean +/- SEM 618.9 +/- 24.0 units/liter versus 719.6 +/- 24.6 units/liter; P = 0.007) and in black lupus patients (991.1 +/- 82.7 units/liter versus 1,164.3 +/- 101.4 units/liter; P = 0.2711). Low PON1 activity in SLE was not associated with the occurrence of aPL, carotid vascular disease, or the use of immunosuppressive drugs. In multiple regression analyses, the Q192R SNP was found to be independently associated with PON1 activity and explained 28% and 41% of the variation in PON1 activity in white patients and black patients, respectively. Stratification of the lupus sample by presence (n = 81) or absence (n = 247) of renal disease revealed significant associations with 3 promoter SNPs, with odds ratios of 3.82 (95% confidence interval [95% CI] 1.49-9.82, P = 0.005), 3.41 (95% CI 1.35-8.61, P = 0.009), and 2.17 (95% CI 1.01-4.68, P = 0.049).
To our knowledge, this is the first study to assess the role of PON1 activity in SLE risk in a large biracial sample from the US. Our data indicate that low PON1 activity determined with paraoxon substrate is independently associated with SLE and that certain PON1 SNPs are associated with lupus nephritis.
已发现以对氧磷为底物测定的血清对氧磷酶1（PON1）活性降低与冠状动脉疾病相关。本研究旨在探讨PON1活性和基因型与系统性红斑狼疮（SLE）风险的关系。
分析了7个PON1单核苷酸多态性（SNP）对380例SLE患者（334例白人，46例黑人）和497例对照（455例白人，42例黑人）的PON1活性、SLE风险、狼疮性肾炎、抗磷脂抗体（aPL）阳性及颈动脉血管疾病的影响。
与对照组相比，白人狼疮患者（平均±标准误618.9±24.0单位/升对719.6±24.6单位/升；P = 0.007）和黑人狼疮患者（991.1±82.7单位/升对1164.3±101.4单位/升；P = 0.2711）以对氧磷为底物的PON1活性均降低。SLE患者PON1活性降低与aPL的发生、颈动脉血管疾病或免疫抑制药物的使用无关。在多元回归分析中，发现Q192R SNP与PON1活性独立相关，分别解释了白人患者和黑人患者PON1活性变异的28%和41%。根据是否存在肾脏疾病（n = 81）或不存在肾脏疾病（n = 247）对狼疮样本进行分层，结果显示与3个启动子SNP存在显著关联，比值比分别为3.82（95%置信区间[95%CI]1.49 - 9.82，P = 0.005）、3.41（95%CI 1.35 - 8.61，P = 0.009）和2.17（95%CI 1.01 - 4.68，P = 0.049）。
据我们所知，这是第一项在美国一个大型双种族样本中评估PON1活性在SLE风险中作用的研究。我们的数据表明，以对氧磷为底物测定的低PON1活性与SLE独立相关，且某些PON1 SNP与狼疮性肾炎相关。
