Correlation of plasma oxidized low-density lipoprotein levels to vascular complications and human serum paraoxonase in patients with type 2 diabetes
Correlation of plasma oxidized low-density lipoprotein levels to vascular complications and human serum paraoxonase in patients with type 2 diabetes
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DOI：
10.1016/j.metabol.2003.10.009
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发表时间：
2004-03-01
影响因子：
9.8
通讯作者：
Hashimoto, K
中科院分区：
文献类型：
--
作者：
Tsuzura, S;Ikeda, Y;Hashimoto, K
低密度脂蛋白（LDL）的氧化修饰在动脉粥样硬化的发生和加速中起着重要作用。人血清对氧磷酶（PON 1）与高密度脂蛋白（HDL）相关，并已显示可降低LDL对脂质过氧化的敏感性。我们研究了循环氧化低密度脂蛋白（Ox-LDL）水平是否与糖尿病血管并发症有关，以及PON 1的酶活性和基因多态性是否影响体内Ox-LDL浓度。合并大血管病变的糖尿病患者与不合并大血管病变的糖尿病患者血浆Ox-LDL浓度无差异。然而，用LDL-胆固醇（OxLDL/LDL-C）或载脂蛋白B（apoB）浓度（Ox-LDL/apoB）校正的Ox-LDL浓度，可能反映了氧化修饰的LDL占总LDL颗粒的比例，在有大血管疾病的患者中显著高于无大血管疾病的患者。此外，周围神经病变患者的Ox-LDL/apoB比值显著高于无此并发症的患者。PON 1基因启动子区-108 C/T多态性的TT基因型与PON 1表达降低相关，其Ox-LDL/apoB比值显著高于TC或CC基因型（TT：0.60 +/- 0.15，CT + CC：0.55 +/- 0.11，P = 0.02）。对Ox-LDL浓度的逐步多元回归分析显示，-108C/T多态性，随后apoB浓度，被确定为显着的贡献者。总之，Ox-LDL/apoB比值与日本2型糖尿病患者的大血管疾病和周围神经病变相关。Ox-LDL/apoB升高可能至少部分是由于糖尿病状态下血清抗氧化能力降低，包括PON 1作用减弱。Ox-LDL/apoB升高可能是糖尿病患者血管并发症易感性的重要标志。(C)2004年爱思唯尔公司All rights reserved.
The oxidative modification of low-density lipoprotein (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and has been shown to reduce the susceptibility of LDL to lipid peroxidation. We investigated whether circulating oxidized LDL (Ox-LDL) levels were associated with diabetic vascular complications, and whether the enzymatic activity and gene polymorphisms of PON1 influenced Ox-LDL concentrations in vivo. There was no difference in the plasma Ox-LDL concentrations between diabetic patients with and without macrovascular diseases. However, Ox-LDL concentrations corrected by LDL-cholesterol (OxLDL/LDL-C) or apolipoprotein B (apoB) concentrations (Ox-LDL/apoB), which probably reflect the proportion of oxidatively modified LDL to total LDL particles, were significantly higher in patients with macrovascular diseases than in those without. In addition, patients with peripheral neuropathy had a significantly higher Ox-LDL/apoB ratio than patients without this complication. The genotype TT of -108C/T polymorphism in the promoter region of the PON1 gene, which is associated with decreased PON1 expression, showed a significantly higher Ox-LDL/apoB ratio than genotypes TC or CC (TT: 0.60 +/- 0.15, CT + CC: 0.55 +/- 0.11, P = .02). Stepwise multiple regression analysis for Ox-LDL concentration revealed that the -108C/T polymorphism, subsequently to apoB concentration, was identified as a significant contributor. In summary, the Ox-LDL/apoB ratio was associated with macrovascular disease and peripheral neuropathy in Japanese patients with type 2 diabetes. Increased Ox-LDL/apoB may result, at least partly, from reduced serum antioxidant capacity in the diabetic state, including the attenuation of PON1 action. Increased Ox-LDL/apoB could be a significant marker for susceptibility to vascular complications in diabetic patients. (C) 2004 Elsevier Inc. All rights reserved.