Tanimoto Noriyasu, Kumon Yoshitaka, Suehiro Tadashi, Ohkubo Susumu, Ikeda Yukio, Nishiya Koji, Hashimoto Kozo
Second Department of Internal Medicine, Kochi Medical School, Kohasu Okoh-Cho, Nankoku, Kochi, 783-8505, Japan.
Life Sci. 2003 May 9;72(25):2877-85. doi: 10.1016/s0024-3205(03)00195-4.
To estimate the alterations of paraoxonase 1 (PON1) and high-density lipoprotein (HDL) in rheumatoid arthritis (RA).
We investigated the serum enzyme activity and concentration of PON1 and their relationship with serum lipids, high-density lipoprotein (HDL) parameters, and acute phase reactants of serum amyloid A (SAA) and C-reactive protein (CRP) in patients with RA.
Serum paraoxonase (PON) activity was significantly decreased in RA patients (n = 64, 131 +/- 53 micro mol/min/L) compared with healthy subjects (n = 155, 164 +/- 59) despite the absence of any difference in serum lipid levels between the two groups. This decrease of serum PON activity in RA patients was found in every genotype (Q/Q, Q/R, R/R) of PON1 at 192 Q/R. There was a different distribution in PON1 Q/R genotypes between RA patients and healthy subjects, and RA patients exhibited less (44%) positive PON1-Q than did the healthy subjects (66%). In a further investigation of age- and gender-matched subgroups of RA (n = 25) and healthy subjects (n = 25), not only serum PON activity, but also lecithin-cholesterol acyltransferase (LCAT) was found to be significantly decreased in RA patients (125 +/- 61 micro mol/min/L, 63.2 +/- 17.2 nmol/ml/hr/37 degrees C) than in healthy subjects (169 +/- 67, 74.7 +/- 19.5), respectively. PON1 and LCAT as well as HDL constituent apolipoprotein (apo) AI and apo AII, were altered significantly in RA patients.
Acute-phase HDL, which is remodeled structurally and functionally in RA, might be less anti-atherogenic due to the impairment of original HDL function. These alterations of HDL in RA patients may explain in part the reported increase in cardiovascular mortality in patients with RA.
评估类风湿关节炎（RA）患者对氧磷酶1（PON1）和高密度脂蛋白（HDL）的变化。
我们研究了RA患者血清中PON1的酶活性和浓度，以及它们与血脂、高密度脂蛋白（HDL）参数、血清淀粉样蛋白A（SAA）和C反应蛋白（CRP）等急性期反应物之间的关系。
尽管两组患者血脂水平无差异，但RA患者（n = 64，131±53微摩尔/分钟/升）血清对氧磷酶（PON）活性显著低于健康受试者（n = 155，164±59）。在192 Q/R位点，RA患者中PON1的每种基因型（Q/Q、Q/R、R/R）血清PON活性均降低。RA患者与健康受试者的PON1 Q/R基因型分布不同，RA患者PON1-Q阳性率（44%）低于健康受试者（66%）。在对年龄和性别匹配的RA亚组（n = 25）和健康受试者亚组（n = 25）的进一步研究中，发现RA患者不仅血清PON活性，而且卵磷脂胆固醇酰基转移酶（LCAT）也显著低于健康受试者，分别为（125±61微摩尔/分钟/升，63.2±17.2纳摩尔/毫升/小时/37℃）和（169±67，74.7±19.5）。RA患者的PON1、LCAT以及HDL成分载脂蛋白（apo）AI和apo AII均有显著改变。
在RA中结构和功能重塑的急性期HDL，可能由于原始HDL功能受损而抗动脉粥样硬化作用减弱。RA患者HDL的这些变化可能部分解释了RA患者心血管死亡率增加的报道。
