MOLECULAR GENETICS ANALYSIS OF APOLIPOPROTEIN H IN SLE

描述：(改编自研究人员摘要)载脂蛋白H(APOH) 是与抗磷脂抗体结合的重要辅因子 阴离子磷脂，表明APOH的结构变化 分子可能对自身抗体与 它们的底物；因此，决定血栓形成的结果。基于 APOH的生理作用及APOH基因的信息 是基因多态的，研究人员假设从基因上 测定磷脂相互作用结合部位的结构变化 对APOH分子的结合有重大影响 抗磷脂自身抗体的亲和力及其相关性 系统性红斑狼疮(SLE)患者的血栓事件。 拟议的全面研究将建立已知的分子基础 基因直接测序的结构和数量多态 APOH基因的表达部分(目标1)；检测新的和常见的基因 APOH基因的多态(AIM 2)；进行体外表达研究 并检测不同APOH等位基因产物与阴离子的结合能力 磷脂(目标3)；比较血浆APOH定量水平 SLE患者和对照组之间的关系(目标4)； APOH多态和血浆APOH定量水平(目标5)；确定 已知APOH基因多态性在系统性红斑狼疮患者和 对照(目标6)；并评估基因定义的 APOH基因结构多态和数量多态， 以及抗磷脂抗体在SLE患者中的发生(目标7)。 调查人员表示，拟议的研究将有助于 APOH基因作用的鉴定与鉴定 SLE患者抗磷脂抗体的基因多态性预测 病人。

DESCRIPTION: (Adapted from Investigator's Abstract) Apolipoprotein H (APOH) is an essential cofactor for the binding of antiphospholipid antibodies to anionic phospholipids, suggesting that structural variations in the APOH molecule may have a significant impact on the binding of autoantibodies to their substrate; thus, determining the outcome of thrombosis. Based upon the current physiologic role of APOH and the information that the APOH gene is genetically polymorphic, the investigators hypothesize that genetically determined structural changes in the phospholipid interaction binding sites on the APOH molecule have a significant impact in determining the binding affinity of antiphospholipid autoantibodies and the occurrence of associated thrombotic events in patients with systemic lupus erythematosus (SLE). The proposed comprehensive study will establish the molecular basis of known structural and quantitative polymorphism by direct sequencing of the expressed portion of the APOH gene (Aim 1); detect new and common genetic polymorphisms in the APOH gene (Aim 2); perform in vitro expression studies and examine the binding abilities of various APOH allele products to anionic phospholipids (Aim 3); compare the quantitative plasma levels of APOH between SLE patients and controls (Aim 4); evaluate the relationship between APOH polymorphisms and quantitative plasma levels of APOH (Aim 5); determine the frequency distributions of known APOH polymorphisms in SLE patients and controls (Aim 6); and evaluate the relationship between genetically defined structural polymorphisms, and quantitative polymorphism in the APOH gene, and the occurrence of antiphospholipid antibodies in SLE patients (Aim 7). The investigators state that the proposed studies will facilitate the identification and characterization of the role of APOH genetic polymorphisms in the prediction of the antiphospholipid antibodies in SLE patients.