Technion Faculty of Medicine, Technion Israel Institute of Technology, 1 Efron Street, Haifa, Israel.
Department of Epidemiology, University of Pittsburgh, 3512 Fifth Avenue, Pittsburgh, PA 15213, USA.
J Diabetes Res. 2018 May 20;2018:6125420. doi: 10.1155/2018/6125420. eCollection 2018.
Haptoglobin (Hp) is an abundant hemoglobin- (Hb-) binding serum protein and a constituent of the HDL proteome. In man, there exists a common polymorphism at the Hp locus with two common alleles defined by the presence (Hp 2 allele) or absence (Hp 1 allele) of a 1.7 kb in-frame partial duplication of exons 3 and 4 of the Hp gene. Numerous studies have demonstrated that the Hp 2-2 genotype is associated with a 3-5-fold increase in vascular disease among individuals with diabetes mellitus (DM). Increased Hp-Hb complex has been shown to be associated with the HDL of Hp 2-2 DM individuals. Hb-associated HDL has been proposed to result in the oxidation of HDL and the consumption of antioxidants in HDL, such as vitamin E, rendering the HDL further susceptible to oxidation. In this study, we set out to identify proteins which become cross-linked to Hb in HDL and to measure vitamin E in HDL as a function of the Hp genotype. We report on the identification of a novel 72 kd Hb reactive species which is cross-linked to HDL and demonstrate that vitamin E in HDL is decreased in Hp 2-2 DM individuals.
触珠蛋白（Hp）是一种丰富的血红蛋白（Hb）结合血清蛋白，也是 HDL 蛋白质组的组成部分。在人类中，Hp 基因座存在一个常见的多态性，由存在（Hp2 等位基因）或不存在（Hp1 等位基因）Hb 基因第 3 和第 4 外显子的 1.7kb 框内部分重复定义。许多研究表明，Hp2-2 基因型与糖尿病患者血管疾病风险增加 3-5 倍相关。已证明增加的 Hp-Hb 复合物与 Hp2-2DM 个体的 HDL 相关。有人提出 Hb 相关的 HDL 会导致 HDL 氧化和 HDL 中抗氧化剂（如维生素 E）的消耗，从而使 HDL 更容易氧化。在这项研究中，我们着手鉴定与 HDL 中的 Hb 发生交联的蛋白质，并测量 Hp 基因型的 HDL 中的维生素 E。我们报告了一种新的 72kD Hb 反应性物质与 HDL 交联的鉴定，并证明 Hp2-2DM 个体的 HDL 中的维生素 E 减少。
